TY - JOUR. T1 - Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis. T2 - The case of histone lysine methyltransferase SET7/9. AU - Wang, Shenglong. AU - Hu, Po. AU - Zhang, Yingkai. PY - 2007/4/12. Y1 - 2007/4/12. N2 - To elucidate enzyme catalysis through computer simulation, a prerequisite is to reliably compute free energy barriers for both enzyme and solution reactions. By employing on-the-fly Born-Oppenheimer molecular dynamics simulations with the ab initio quantum mechanical/molecular mechanical approach and the umbrella sampling method, we have determined free energy profiles for the methyl-transfer reaction catalyzed by the histone lysine methyltransferase SET7/9 and its corresponding uncatalyzed reaction in aqueous solution, respectively. Our calculated activation free energy barrier for the enzyme catalyzed reaction is 22.5 kcal/mol, which agrees very well with the experimental value of 20.9 kcal/mol. The difference in potential of mean ...

We use a wide spectrum of state-of-the-art computational techniques, including explicit solvent molecular dynamics simulations, advanced ab initio quantum-chemical calculations and modern bioinformatics.. The main research aim is to provide unique insights into the role of molecular interactions in structure, dynamics, function and evolution of nucleic acids. In that sense, advanced computations can substantially complement experimental techniques. Our research is highly interdisciplinary and we wish to bring modern physical-chemistry insights into structural and molecular biology, biochemistry and bioinformatics. Our research has impact also in some other areas of chemistry, such as physical, supramolecular and bioinorganic chemistry.. Ab initio quantum chemical (QM) technique is state of the art physical-chemistry methodology that provides accurate and physically complete description of small model systems. The technique reveals direct structure - energy relations that cannot be obtained by ...

We use a wide spectrum of state-of-the-art computational techniques, including explicit solvent molecular dynamics simulations, advanced ab initio quantum-chemical calculations and modern bioinformatics.. The main research aim is to provide unique insights into the role of molecular interactions in structure, dynamics, function and evolution of nucleic acids. In that sense, advanced computations can substantially complement experimental techniques. Our research is highly interdisciplinary and we wish to bring modern physical-chemistry insights into structural and molecular biology, biochemistry and bioinformatics. Our research has impact also in some other areas of chemistry, such as physical, supramolecular and bioinorganic chemistry.. Ab initio quantum chemical (QM) technique is state of the art physical-chemistry methodology that provides accurate and physically complete description of small model systems. The technique reveals direct structure - energy relations that cannot be obtained by ...

The objective of this chapter is to describe how equilibrium molecular dynamics simulations (with the help of harmonic lattice dynamics calculations) can be used to predict phonon properties and thermal conductivity using normal mode decomposition. The molecular dynamics and lattice dynamics methods are reviewed and the normal mode decomposition technique is described in detail. The application of normal mode decomposition is demonstrated through case studies on crystalline, alloy, and amorphous Lennard-Jones phases. Notable works that used normal mode decomposition are presented and the future of molecular dynamics simulations in phonon transport modeling is discussed.. ...

TY - JOUR. T1 - Phonon modes in single-walled molybdenum disulphide nanotubes. T2 - Lattice dynamics calculation and molecular dynamics simulation. AU - Jiang, Jin Wu. AU - Wang, Bing Shen. AU - Rabczuk, Timon. PY - 2014/3/14. Y1 - 2014/3/14. N2 - We study the phonon modes in single-walled MoS2 nanotubes via lattice dynamics calculation and molecular dynamics simulation. The phonon spectra for tubes of arbitrary chiralities are calculated from a dynamical matrix constructed by the combination of an empirical potential with the conserved helical quantum numbers (κ, n). In particular, we show that the frequency (ω) of the radial breathing mode is inversely proportional to the tube diameter (d) as ω = 665.3/d cm-1. The eigenvectors of the twenty lowest-frequency phonon modes are illustrated. Based on these eigenvectors, we demonstrate that the radial breathing oscillation is initially disturbed by phonon modes of three-fold symmetry, then eventually the tube is squashed by modes of two-fold ...

Based on molecular dynamics simulations, an analysis of structure and dynamics is performed on interfacial water at a liquid crystalline dipalmitoylphosphatidycholine/water system. Water properties relevant for understanding NMR relaxation are emphasized. The first and second rank orientational order parameters of the water O-H bonds were calculated, where the second rank order parameter is in agreement with experimental determined quadrupolar splittings. Also, two different interfacial water regions (bound water regions) are revealed with respect to different signs of the second rank order parameter. The water reorientation correlation function reveals a mixture of fast and slow decaying parts. The fast (ps) part of the correlation function is due to local anisotropic water reorientation whereas the much slower part is due to more complicated processes including lateral diffusion along the interface and chemical exchange between free and bound water molecules. The 100-ns-long molecular dynamics ...

The vibrational behavior of single-walled carbon nanocones is studied using molecular structural method and molecular dynamics simulations. In molecular structural approach, point mass and beam elements are employed to model the carbon atoms and the connecting covalent bonds, respectively. Single-walled carbon nanocones with different apex angles are considered. Besides, the vibrational behavior of nanocones under various types of boundary conditions is studied. Predicted natural frequencies are compared with the existing results in the literature and also with the ones obtained by molecular dynamics simulations. It is found that decreasing apex angle and the length of carbon nanocone results in an increase in the natural frequency. Comparing the vibrational behavior of single-walled carbon nanocones under different boundary conditions shows that the effect of end condition on the natural frequency is more prominent for nanocones with smaller apex angles.

We use a single molecule atomic force spectroscopy combined with the steered molecular dynamics simulation to determine a mechanical behavior of neural cell adhesion protein contactin during its unfolding. Force curves typical for modular proteins were observed, showing at most four unfolding peaks. The analysis of force spectra performed within worm-like chain model of polymer elasticity showed the presence of three unfolding lengths. Small plateaus, most likely resulting from forced transitions within domains were observed for the first time. Steered molecular dynamics simulations help to determine atomistic picture of domain unfolding ...

The morphologies of heterogeneous clusters of polycyclic aromatic hydrocarbons (PAHs) are investigated using molecular modelling. Clusters of up to 100 molecules containing combinations of the different sized PAHs circumcoronene, coronene, ovalene, or pyrene are evaluated. Replica exchange molecular dynamics simulations using an all-atom force field parameterised for PAHs sample many configurations at high and low temperatures to determine stable low energy structures. The resulting cluster structures are evaluated using molecular radial distances and coordination numbers, and are found to be independent of initial configuration and the cluster sizes studied. Stable clusters consist of stacked PAHs in a core-shell structure, where the larger PAHs are found closer to the cluster core and the smaller PAHs are located on the cluster surface. This work provides novel insight into the molecular partitioning of heterogeneous aromatic clusters, with particular relevance to the structure of nascent soot ...

TY - JOUR. T1 - Molecular dynamics simulation of atomic-scale frictional behavior of corrugated nano-structured surfaces. AU - Kim, Hyun Joon. AU - Kim, Dae Eun. PY - 2012/7/7. Y1 - 2012/7/7. N2 - Surface morphology is one of the critical parameters that affect the frictional behavior of two contacting bodies in relative motion. It is important because the real contact area as well as the contact stiffness is dictated by the micro- and nano-scale geometry of the surface. In this regard, the frictional behavior may be controlled by varying the surface morphology through nano-structuring. In this study, molecular dynamics simulations were conducted to investigate the effects of contact area and structural stiffness of corrugated nano-structures on the fundamental frictional behavior at the atomic-scale. The nano-structured surface was modeled as an array of corrugated carbon atoms with a given periodicity. It was found that the friction coefficient of the nano-structured surface was lower than ...

AbstractThe aim of this thesis is to investigate the structural and thermodynamic properties of biologically and technological relevant macromolecules when placed at soft interfaces. In particular two amphiphilic macromolecules characterized by different topologies have been investigated namely amphiphilic dendrimers and linear block copolymers. This goal is achieved using a multiscale approach which includes all-atom, united atom and coarse grained models by means of molecular dynamic simulations.Amphiphilic dendrimers have shown to be promising building blocks for a range of interfacial materials and can be used in applications such as surface-base sensors or surface nanopatterning. In this part of the thesis by means of all-atom molecular dynamics simulations, we investigated the structure and stability of alkyl-modified polyamido-amide (PAMAM) dendrimers at the air/water interface as a function of the number and the relative position of the modified end groups. We found that the PAMAM ...

AmtB is one of the ammonium transporter proteins facilitating the ammonium transport across the cellular membranes. Experimentally, the substrate used in in vitro studies is the radio labeled [14C]methylammonium, rather than ammonium itself. To explore the similarity and difference of the conduction mechanism of methylamine and ammonia molecules through AmtB, molecular dynamics simulations on 22 carefully designed systems were performed, which demonstrated that methylamine could be automatically transported in a very similar way to ammonia. The driving force for the conduction is mainly the hydrogen bond network comprising His168, His318, and Tyr32, working in coordination with NH−π interaction with residue Trp212. Then, Ser263 translocated the substrates from the exit gate into the cytoplasm by hydrogen bond interaction.The aromatic ring of Trp212 acted like a springboard to facilitate the translocation of the substrates from site Am2 to Am4 via NH−π interaction. Without the mediation of ...

The data here provides the raw data for the calculations of radial distribution functions, hydrogen bond analysis, lateral lipid diffusion and lipid tail order parameters. This raw data was generated using tools from the CPPTRAJ analysis package which is freely available with the AmberTools program (https://ambermd.org/AmberTools.php). The data presented here shows how two drug molecules (propofol and fentanyl) alter the physical and mechanical properties of DOPC and DPPC lipid bilayers, and for the first time, how a general anesthetic and an opioid analgesic/anesthetic differ in their interactions with phospholipid membranes, by direct comparison. Understanding the differences between opioid and anesthetic interactions with phospholipid bilayers will lead to a more complete understanding of general anesthesia at the molecular level ...

TY - JOUR. T1 - Surface structure of methanol/water solutions via sum frequency orientational analysis and molecular dynamics simulation. AU - Ishihara, Takashi. AU - Ishiyama, Tatsuya. AU - Morita, Akihiro. N1 - Publisher Copyright: © 2015 American Chemical Society.. PY - 2015/5/7. Y1 - 2015/5/7. N2 - Polarization dependence of sum frequency generation (SFG) spectroscopy has been widely discussed to detect molecular orientation at surfaces. The present work examines the orientational analysis by molecular dynamics (MD) simulation of methanol/water mixture surfaces with varying concentrations. We calculated by MD the surface structure of the solutions and their SFG spectra in the methyl C-H stretching region, and directly analyzed the relations. The MD calculations reported that (i) the SFG signal of the methyl symmetric stretching exhibits a turnover behavior with increasing concentration and (ii) the polarization ratio is almost invariant over the concentration, while (iii) the orientation of ...

Molecular dynamics (MD) simulation of protein helps to study motion and its development with time which may not be studied experimentally. Because of the tremendous advancement in hardware and software computer technologies in recent years, longer and more realistic molecular dynamics (MD) simulations of a protein are possible now in reasonable periods of time. In this presentation, Dr. Thapa explains how he has used molecular dynamics to conduct research on the Norwalk virus, a major cause of epidemic gastroenteritis in humans ...

Abstract: A series of molecular dynamics simulations for the structure transformation during heating and melting of FCC Ni have been performed with the Tight-binding potential developed by Cleri and Rosato. The simulated melting point of Ni at constant pressure condition is between 1850 K and 1900 K. The static structural informations, such as the radial distribution functions and the distributions of the coordination numbers, have been obtained during the simulation. The calculated diffusion coefficient of the liquid Ni is about 5.02×10−9 m2•s−1 at 1900 K, which is consistent with the experimental result. The possible distortion of local structure of FCC crystal and the relevant changes of the types of the atom pairs (indexed by Honeycutt-Anderesen pair analysis technique) have been analyzed. The distributions of the short-range ordered (SRO) structures of FCC and defective icosahedra at different temperatures are calculated combining the local configuration search and H-A pair analysis ...

Here, we perform molecular dynamics simulation on cubic ZrO 2 and yttria-stabilized zirconia (YSZ) to elucidate defect cluster formation resulting from radiation damage, and evaluate the impact of Y-dopants. Interstitial clusters composed of split-interstitial building blocks, i.e., Zr-Zr or Y-Zr are formed. Moreover, oxygen vacancies control cation defect migration; in their presence, Zr interstitials aggregate to form split-interstitials whereas in their absence Zr interstitials remain immobile, as isolated single-interstitials. Y-doping prevents interstitial cluster formation due to sequestration of oxygen vacancies. ...

Single particle cryoEM has emerged as a powerful method for structure determination of proteins and complexes, complementing X-ray crystallography and NMR spectroscopy. Yet, for many systems, the resolution of cryoEM density map has been limited to 4-6 Å, which only allows for resolving bulky amino acids side chains, thus hindering accurate model building from the density map. On the other hand, experimental chemical shifts (CS) from solution and solid state MAS NMR spectra provide atomic level data for each amino acid within a molecule or a complex; however, structure determination of large complexes and assemblies based on NMR data alone remains challenging. Here, we present a novel integrated strategy to combine the highly complementary experimental data from cryoEM and NMR computationally by molecular dynamics simulations to derive an atomistic model, which is not attainable by either approach alone. We use the HIV-1 capsid protein (CA) C-terminal domain as well as the large capsid assembly to

Molecular dynamics simulations were performed to elucidate the interactions of CDK2 and CDK5 complexes with three inhibitors: R-roscovitine, S-roscovitine, and indirubin-3′-oxime. The preference of the two complexes for R-roscovitine over the S enantiomer, as reported by the experiment, was also found by the simulations. More importantly, the simulations showed that the cause of the stronger affinity for the R enantiomer is the presence of an important hydrogen bond between R-roscovitine and the kinases not found with S-roscovitine. The simulations also showed two amino acid mutations in the active site of CDK5/R-roscovitine that favor binding-enhanced electrostatic contributions, making the inhibitor more effective for CDK5 than for CDK2. This suggests that the effectiveness of roscovitine-like inhibitors can be improved by enhancing their electrostatic interaction with the kinases. Finally, molecular mechanics-Possion-Boltzmann/surface area calculations of the CDK5/indirubin-3′-oxime ...

NrdH-redoxins shuffle electrons from the NADPH pool in the cell to Class Ib ribonucleotide reductases, which in turn provide the precursors for DNA replication and repair. NrdH-redoxins have a CVQC active site motif and belong to the thioredoxin-fold protein family. As for other thioredoxin-fold proteins, the pK(a) of the nucleophilic cysteine of NrdH-redoxins is of particular interest since it affects the catalytic reaction rate of the enzymes. Recently, the pK(a) value of this cysteine in Corynebacterium glutamicum and Mycobacterium tuberculosis NrdH-redoxins were determined, but structural insights explaining the relatively low pK(a) remained elusive. We subjected C. glutamicum NrdH-redoxin to an extensive molecular dynamics simulation to expose the factors regulating the pK(a) of the nucleophilic cysteine. We found that the nucleophilic cysteine receives three hydrogen bonds from residues within the CVQC active site motif. Additionally, a fourth hydrogen bond with a lysine located N-terminal ...

Author: Verde, Ana Vila et al.; Genre: Journal Article; Published in Print: 2009-08; Title: Investigating the Specificity of Peptide Adsorption on Gold Using Molecular Dynamics Simulations

Article Molecular dynamics simulations of breaking metallic nanowires. In the present work, we have reviewed the importance of conductance histograms as an experimental tool able to address the statistical behaviour of the electronic transport throug...

Fingeraftryk Dyk ned i forskningsemnerne om A new transferable interatomic potential for molecular dynamics simulations of borosilicate glasses. Sammen danner de et unikt fingeraftryk. ...

Understanding interactions between functionalized gold nanoparticles (NPs) and lipid bilayers is essential for their use in biomedical applications. Experiments and continuum-scale simulations have suggested that small (~5 nm diameter) cationic NPs aggregate when adsorbed to the surface of zwitterionic lipid bilayers despite being stable in aqueous solution, suggesting that bilayer-mediated interactions facilitate assembly. Determining the origin of these effects and the impact of other bilayer features, such as lipid phase separation, on the interfacial assembly of NPs would enable the design of NPs for applications that require NP assembly, such as photothermal therapy.. In this work, we use chemically specific coarse-grained molecular dynamics simulations to show that cationic NP adsorption to lipid bilayers is driven by a balance between favorable NP-lipid interactions and the unfavorable mechanical deformation of the bilayer to create local curvature. The minimization of induced curvature ...

The influenza virus is surrounded by an envelope composed of a lipid bilayer and integral membrane proteins. Understanding the structural dynamics of the membrane envelope provides biophysical insights into aspects of viral function, such as the wide-ranging survival times of the virion in different environments. We have combined experimental data from X-ray crystallography, nuclear magnetic resonance spectroscopy, cryo-electron microscopy, and lipidomics to build a model of the intact influenza A virion. This is the basis of microsecond-scale coarse-grained molecular dynamics simulations of the virion, providing simulations at different temperatures and with varying lipid compositions. The presence of the Forssman glycolipid alters a number of biophysical properties of the virion, resulting in reduced mobility of bilayer lipid and protein species. Reduced mobility in the virion membrane may confer physical robustness to changes in environmental conditions. Our simulations indicate that viral spike

Fingerprint Dive into the research topics of Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Together they form a unique fingerprint. ...

I will discuss methods for spatio-temporal modelling in molecular and cell biology, including all-atom and coarse-grained molecular dynamics (MD) and stochastic reaction-diffusion models, with the aim of developing and analysing multiscale methods which use MD simulations in parts of the computational domain and (less-detailed) stochastic reaction-diffusion approaches in the remainder of the domain. The main goal of this multiscale methodology is to use a detailed modelling approach in localized regions of particular interest (in which accuracy and microscopic details are important) and a less detailed model in other regions in which accuracy may be traded for simulation efficiency. Applications using all-atom MD include intracellular dynamics of ions and ion channels. Applications using coarse-grained MD include protein binding to receptors on the cellular membrane, where modern stochastic reaction-diffusion simulators of intracellular processes can be used in the bulk and a ccurately coupled ...

Dr. Shepherd spent the first 12 years of her academic career at Westminster College, Salt Lake City, UT before joining the faculty at St. Edwards, Fall 2014. She leads workshops offered nationwide on both facilitating POGIL in the classroom and incorporating theoretical and computational chemistry into the undergraduate chemistry curriculum. Her research efforts with undergraduates involve the use of coarse-grained molecular dynamics simulations to study aqueous systems at the nanoscale. She is a member of MERCURY (Molecular Education and Research Consortium in Undergraduate computational chemistRY) and advocates for the use of technology in meaningful ways to enhance student learning.. ...

figure, Normal mode analysis aims at explaining the internal motions of a protein. Molecular Dynamics simulations are only capable of simulation very short amount of times (pico seconds). They are very compuationally demanding, since the motion of each atom is calculated with an energy function. The native state of a protein actually represents an ensemble of microstates which contain the overall fold and the same secondary structure elements, but differ in the local atomic coordinates. The microstates are thought to represent fluctuations around the well-defined equilibrium native structure. In this sense, large conformational changes of proteins can be monitored that occur within these defined microstates. These low level conformational changes take much longer (nano seconds) and thus are not accessible by standard molecular dynamics simulation. But they can be addressed by normal mode analysis, where only movements of backbone atoms are considered. The underlying assumption for the ...

figure, Normal mode analysis aims at explaining the internal motions of a protein. Molecular Dynamics simulations are only capable of simulation very short amount of times (pico seconds). They are very compuationally demanding, since the motion of each atom is calculated with an energy function. The native state of a protein actually represents an ensemble of microstates which contain the overall fold and the same secondary structure elements, but differ in the local atomic coordinates. The microstates are thought to represent fluctuations around the well-defined equilibrium native structure. In this sense, large conformational changes of proteins can be monitored that occur within these defined microstates. These low level conformational changes take much longer (nano seconds) and thus are not accessible by standard molecular dynamics simulation. But they can be addressed by normal mode analysis, where only movements of backbone atoms are considered. The underlying assumption for the ...

Sasselli, I. R. and Moreira, I. P. and Ulijn, R. V. and Tuttle, T. (2017) Molecular dynamics simulations reveal disruptive self-assembly in dynamic peptide libraries. Organic and Biomolecular Chemistry. ISSN 1477-0520 Casals-Cruañas, Èric and Gonzalez-Belman, Oscar F. and Besalú-Sala, Pau and Nelson, David James and Poater, Albert (2017) The preference for dual-gold(I) catalysis in the hydro(alkoxylation vs phenoxylation) of alkynes. Organic and Biomolecular Chemistry. pp. 1-10. ISSN 1477-0520 Cumine, Florimond and Zhou, Shengze and Tuttle, Tell and Murphy, John A. (2017) A study of diketopiperazines as electron-donor initiators in transition metal-free haloarene-arene coupling. Organic and Biomolecular Chemistry, 15. 3324 - 3336. ISSN 1477-0520 McPherson, Christopher G. and Caldwell, Nicola and Jamieson, Craig and Simpson, Iain and Watson, Allan J. B. (2017) Amidation of unactivated ester derivatives mediated by trifluoroethanol. Organic and Biomolecular Chemistry. ISSN 1477-0520 Emery, ...

Tailoring the thermal conductivity of polymers is central to enlarge their applications in the thermal management of flexible integrated circuits. Progress has been made over the past decade by fabricating materials with various nanostructures, but a clear relationship between various functional groups and thermal properties of polymers remains to be established. Here, we numerically study the thermal conductivity of single-stranded carbon-chain polymers with multiple substituents of hydrogen atoms through atomic mass modification. We find that their thermal conductivity can be tuned by atomic mass modifications as revealed through molecular dynamics simulations. The simulation results suggest that heavy homogeneous substituents do not assist heat transport and trace amounts of heavy substituents can in fact hinder heat transport substantially. Our analysis indicates that carbon chain has the biggest contribution (over 80%) to the thermal conduction in single-stranded carbon-chain polymers. We ...

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is slightly less ...

Detailed understanding of lipid bilayers are of tremendous importance due to their role in many biological processes. This Thesis focuses on structural and dynamical properties of lipid bilayers and their interactions with locally acting anesthetics, studied by Molecular Dynamics simulations.. The effect of dehydration of a lipid bilayer is a biologically important phenomenon which was investigated by detailed examination of a number of structural and dynamical lipid parameters at different levels of hydration. The result shows that whereas the structural properties of the bilayer only moderately depend on the degree of hydration, the dynamics of the system is affected very strongly.. Related to changes in the bilayer caused by hydration are structural and dynamical changes caused by the presence of anesthetics. Lidocaine is a common, locally acting anesthetic that interacts with lipid bilayers. The difference in position, orientation and diffusional behavior for charged and uncharged lidocaine ...

Zeolites are porous silicate materials with pore sizes similar to industrially important molecules (water, carbon dioxide, hydrogen, etc.). Zeolites are used in gas separation (due to their sieving effect), catalysis (due to their shape selectivity), adsorption, and other applications. In the Tsapatsis group, zeolite nanoparticles with lamellar morphologies (zeolite nanosheets) are developed for gas separation, and catalysis. They have also published the use of 2D zeolites to form the thinnest zeolite films ever reported on porous and non porous supports. Because of the thin dimension of the nanosheets, the zeolite nanosheets give higher flux for gas separation applications, and enhance diffusion in catalysis.. The group is currently examining the water-ethanol separation through these membranes. The modeling work requires adsorption coefficients and diffusion coefficients. These coefficients are obtained through molecular dynamics simulations and the researchers are currently in progress to ...

Flexible reduced graphene oxide (rGO) sheets are being considered for applications in portable electrical devices and flexible energy storage systems. However, the poor mechanical properties and electrical conductivities of rGO sheets are limiting factors for the development of such devices. Here we use MXene (M) nanosheets to functionalize graphene oxide platelets through Ti-O-C covalent bonding to obtain MrGO sheets. A MrGO sheet was crosslinked by a conjugated molecule (1-aminopyrene-disuccinimidyl suberate, AD). The incorporation of MXene nanosheets and AD molecules reduces the voids within the graphene sheet and improves the alignment of graphene platelets, resulting in much higher compactness and high toughness. In situ Raman spectroscopy and molecular dynamics simulations reveal the synergistic interfacial interaction mechanisms of Ti-O-C covalent bonding, sliding of MXene nanosheets, and π-π bridging. Furthermore, a supercapacitor based on our super-tough MXene-functionalized graphene sheets

In order to make the model more computationally efficient it has to be simplified. First and most natural simplification concerns the treatment of the solvent. In contrast to explicit solvent, which treats every water molecule in atomic detail, implicit solvent represents the effect of water molecules through effective potentials acting on the protein. As a consequence, a large reduction in the total number of degrees of freedom in the simulated system is achieved. In the present work, simulations with implicit solvent model ran about five times faster than the equivalent explicit solvent model, allowing us to extend the total simulation time by that amount. Another benefit of treating solvent implicitly is accelerated conformational dynamics of the protein. In explicit solvents, the dynamics of solute molecules is controlled by the solvents viscosity or internal friction. The magnitude of the friction is used as a parameter in implicit solvent simulations and thus can be varied to obtain ...

In this article we review the key modeling tools available for simulating biomolecular systems. We consider recent developments and representative applications of mixed quantum mechanics/molecular mechanics (QM/MM), elastic network models (ENMs), coarse-grained molecular dynamics, and grid-based tools for calculating interactions between essentially rigid protein assemblies. We consider how the different length scales can be coupled, both in a sequential fashion (e.g. a coarse-grained or grid model using parameterization from MD simulations), and via concurrent approaches, where the calculations are performed together and together control the progression of the simulation. We suggest how the concurrent coupling approach familiar in the context of QM/MM calculations can be generalized, and describe how this has been done in the CHARMM macromolecular simulation package.

In collaboration with Clariant Oil Services, Clariant Produkte (Deutschland) and the Centre for Research & Technology Hellas (CERTH), researchers from Nextmol have published the paper Size dependence of the dissociation process of spherical hydrate particles via microsecond molecular dynamics simulations in the journal Physical Chemistry Chemical Physics (PCCP) of the Royal Society of Chemistry.. The paper, published as a Communication, investigates the dissociation process of spherical sII mixed methane-propane hydrate particles in liquid hydrocarbon via microsecond-long molecular dynamics simulations. A strong dependence of the melting temperature on the particle size has been found. Furthermore, analysis in the context of the Gibbs-Thomson effect has provided new insights into the fundamental properties of gas hydrates, such as the estimation of the melting temperature of a flat hydrate surface (bulk hydrate), the calculation of the surface tension between hydrate and hydrocarbon, and the ...

The serotonin transporter (SERT) exists as the primary target for treating depression. We are conducting free energy calculations to find potential inhibitors of SERT. Absolute binding free energy calculations will accurately calculate the binding energy of protein-ligand complexes. Compounds that result in favorable free energy calculations are synthesized and experimental binding assays are performed to validate the calculations. These calculations will help in improving rational drug design by employing computational methods that will aid in understanding drug recognition in treating CNS disorders such as depression, anxiety, and ADHD.. Bernandie Jean, Graduate Student. ...

Finding Conformational Transition Pathways from Discrete Molecular Dynamics Simulations, Sfriso, Pedro, Emperador Agustí, Orellana Laura, Hospital Adam, Gelpí Josep-Lluis, and Orozco Modesto , Journal of Chemical Theory and Computation, 2012/11/13, Volume 8, p.4707 - 4718, (2012) ...

Read the book An Introduction To Markov State Models And Their Application To Long Timescale Molecular Simulation by Gregory R. Bowman ; Vijay S. Pande ; Frank Noé, Ed online or Preview the book. Please wait while, the book is loading ...

Atomistic simulations have the potential to elucidate the molecular basis of biological processes such as protein misfolding in Alzheimers disease or the conformational changes that drive transcription or translation. However, most simulations can only capture the nanosecond to microsecond timescale, whereas most biological processes of interest occur on millisecond and longer timescales. Also, even with an infinitely fast computer, extracting meaningful insight from simulations is difficult because of the complexity of the underlying free energy landscapes. Fortunately, Markov State Models (MSMs) can help overcome these limitations.. MSMs may be used to model any random process where the next state depends solely on the current state. For example, imagine exploring New York City by rolling a die to randomly select which direction to go in each time you came to an intersection. Such a process could be described by an MSM with a state for each intersection. Each state might have a probability of ...

Huntington disease is a neurodegenerative disease characterized by a polymorphic tract of polyglutamine repeats in exon 1 of the huntingtin protein, which is thought to be responsible for protein aggregation and neuronal death. The polyglutamine tract is preceded by a 17-residue sequence that is intrinsically disordered. This region is subject to phosphorylation, acetylation and other post-translational modifications in vivo, which modulate its secondary structure, aggregation and, subcellular localization. We used Molecular Dynamics simulations with a novel Hamiltonian-replica-exchange-based enhanced sampling method, SWISH, and an optimal combination of water and protein force fields to study the effects of phosphorylation and acetylation as well as cross-talk between these modifications on the huntingtin N-terminus. The simulations, validated by circular dichroism, were used to formulate a mechanism by which the modifications influence helical conformations. Our findings have implications for

Catalytic alkene cracking on H-ZSM-5 involves a complex reaction network with many possible reaction routes and often elusive intermediates. Herein, advanced molecular dynamics simulations at 773 K, a typical cracking temperature, are performed to clarify the nature of the intermediates and to elucidate dominant cracking pathways at operating conditions. A series of C4-C8 alkene intermediates are investigated to evaluate the influence of chain length and degree of branching on their stability. Our simulations reveal that linear, secondary carbenium ions are relatively unstable, although their lifetime increases with carbon number. Tertiary carbenium ions, on the other hand, are shown to be very stable, irrespective of the chain length. Highly branched carbenium ions, though, tend to rapidly rearrange into more stable cationic species, either via cracking or isomerization reactions. Dominant cracking pathways were determined by combining these insights on carbenium ion stability with intrinsic ...

The mechanism by which chiral selectivity takes place is complicated by the surface morphology, the possible involvement of the solvent, and the characteristics of the chiral molecules at the surface. My goal is to model and understand the factors which lead to significant discrimination in the case of three closely related chiral stationary phases: N-(1-phenylethyl)-N-[3-(triethoxysilyl)propyl]-urea (PEPU), [(3,5-dinitrobenzoyl)-amino]-N-[3-(triethoxysilyl)propyl]-2-phenylacetamide (DNB-phenyglycine), and [(3,5-dinitrobenzoyl)amino]-N-[3-(triethoxysilyl)propyl]-4-methylpentanamide (DNB-leucine). Ab initio calculations are used to develop molecular models of these chiral selectors. These models are employed in molecular dynamics (MD) simulations, which provide the theoretical framework for modelling chiral interfaces in different solvent mixtures. The MD simulations of PEPU interfaces show that, in alcohol/water mixtures, the alcohols form domains at the interface with the hydrophobic portions ...

We present parallel algorithms for molecular dynamics, which are suitable for a small number of processors. These parallel methods are based on a spatial decomposition of the simulation box, that takes advantage of a linked-cell list. The test of the algorithms is conducted, in the case of the Axilrod-Teller fluid at constant pressure, by evaluating the speed-up induced by the various communications schemes involved. These methods seem promising for studying complex physical properties, i.e. the dynamics of the glassy states and the structure at liquid- solid interface, which requires respectively long time scale simulations on small systems and large simulation boxes ...

The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α

Although the structure of Human Pancreatic Lipase has been documented through the X-ray crystallography, the knowledge about the molecular rearrangement and dynamic equilibrium in the structure (particularly in the catalytic triad and lid domains) is very scanty. The structural fluctuations and conformational changes undergo by Human Pancreatic Lipase (HPL) with and without colipase were computationally investigated through molecular dynamics simulation technique using GROMACS 2018.4, MOE 2016.0801 and VMD softwares in order to gain insight into the complex transitions at different domains. The structural stability was revealed vis-a-vis Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) plots. The levels of compactness/folding and conformational changes of the protein were determined using Radius of gyration and secondary analysis respectively. Salt bridge analysis gives more ionic pairs interactions than experimentally determined results. Results show that though both proteins

Molecular dynamics simulations were used to investigate trends in noble gas (Ar, Kr, Xe) diffusion in the metal-organic frameworks HKUST-1 and ZIF-8. Diffusion occurs primarily through inter-cage jump events, with much greater diffusion of guest atoms in HKUST-1 compared to ZIF-8 due to the larger cage and window sizes in the former. We compare diffusion coefficients calculated for both rigid and flexible frameworks. For rigid framework simulations, in which the framework atoms were held at their crystallographic or geometry optimized coordinates, sometimes dramatic differences in guest diffusion were seen depending on the initial framework structure or the choice of framework force field parameters. When framework flexibility effects were included, argon and krypton diffusion increased significantly compared to rigid-framework simulations using general force field parameters. Additionally, for argon and krypton in ZIF-8, guest diffusion increased with loading, demonstrating that guest-guest ...

Computer-Aided Drug Design ??An Overview -- Prediction of Human Drug Targets and their Interactions Using Machine Learning Methods: Current and Future Perspectives -- Practices in Molecular Docking and Structure-based Virtual Screening -- Phylogenetic and Conservation Based Approaches to Predict Protein Functional Sites -- De novo design of Ligands using Computational Methods -- Molecular Dynamics Simulation and the Prediction of Druggable Binding Sites -- Virtual Ligand Screening using PL-PatchSurfer2, a Molecular Surface-based Protein-ligand Docking Method -- Fragment Based Ligand Designing -- Molecular Dynamics as a Tool for Virtual Ligand Screening -- Building Molecular Interaction Networks from Microarray Data for Drug Target Screening -- Absolute Alchemical Free Energy Calculations for Ligand Binding -- Evaluation of Protein-ligand Docking by Cyscore -- Molecular Dynamics Simulations of Protein-drug Complexes:혻 A Computational Protocol for Investigating the Interactions of Small-Molecule ...

TY - JOUR. T1 - Structure of water saturated CTMA-montmorillonite hybrid: Molecular dynamics simulation investigation. AU - Zhu, Runliang. AU - Shapley, Thomas V. AU - Molinari, Marco. AU - Ge, Fei. AU - Parker, Stephen C. N1 - Advances in Materials REsearch Vol 233-235: Fundamental of Chemical Engineering. Conference article from 2011 International Conference on Chemical Engineering and Advanced Materials, CEAM 2011. 28-30 May 2011. Changsha, China.. PY - 2011. Y1 - 2011. N2 - Molecular dynamics (MD) simulations have been used to investigate the interlayer structure of water saturated organoclays. The basal spacing values of cetyltrimethylammonium (CTMA) intercalated montmorillonite (CTMA-Mont) in dry and water saturated states were detected using XRD. Then the results were compared with simulation results of dry CTMA-Mont. The MD simulations show that the CTMA cations form layer structures on siloxane surface and aggregate in the interlayer space. Water molecules can access part of the ...

The overall aim of this study is to calculate some water properties in the single wall carbon naotubes (SWCNT) and compare them to the bulk water properties to investigate the deviation of water properties inside the SWCNT from those in the bulk. Here some physical and transport properties of water molecules in the single wall carbon nanotube were reported by performing molecular dynamics (MD) simulation. Radial and axial density; hydrogen bond numbering; hydrogen bond distribution and diffusivity of water molecules inside the SWCNT were calculated. Results have good agreements with other researcher results. These calculations show that molecular dynamics simulation would be a reasonable method to analyze the properties of the new nanoscale systems.

We study the intrinsic nature of the finite system-size effect in estimating shear viscosity of dilute and dense fluids within the framework of the Green-Kubo approach. From extensive molecular dynamics simulations, we observe that the size effect on shear viscosity is characterized by an oscillatory behavior with respect to system size L at high density and by a scaling behavior with an L-1 correction term at low density. Analysis of the potential contribution in the shear-stress autocorrelation function reveals that the former is configurational and is attributed to the inaccurate description of the long-range spatial correlations in finite systems. Observation of the long-time inverse-power decay in the kinetic contribution confirms its hydrodynamic nature. The L-1 correction term of shear viscosity is explained by the sensitive change in the long-time tail obtained from a finite system ...

The ab initio molecular dynamics simulations are performed to study the atomic structures of Co92-xBxTa8 (x = 30, 32.5, 35, 37.5, at.%) glassy alloys. The result shows that the local packing of B-centered clusters is more efficient than that for Co- a

Paper title: Molecular Dynamics Simulations of Osmosis and Reverse Osmosis in Solutions Journal: Adsorption 2, 95-101 (1996) Author: S. Murad Chemical Engineering Department, University of Illinois in Chicago, Chicago IL 60607, USA Summary: Using molecular dynamics, the paper investigated what happens during osmosis, reverse osmosis and the transition between them. By...

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TY - JOUR. T1 - Molecular dynamics study on external field induced crystallization of amorphous argon structure. AU - Park, Seungho. AU - Cho, Sung San. AU - Lee, Joon Sik. AU - Choi, Young Ki. AU - Kwon, Ohmyoung. PY - 2004/11. Y1 - 2004/11. N2 - A molecular dynamics study has been conducted on an external-force-field- induced isothermal crystallization process of amorphous structures as a new low-temperature athermal crystallization process. An external cyclic-force field with a dc bias is imposed on molecules selected randomly in an amorphous-phase of argon. Multiple peaks smoothed out in the radial distribution functions for amorphous states appear very clearly during the crystallization process that cannot be achieved otherwise. When the amorphous material is locally exposed to an external force field, crystallization starts and propagates from the interfacial region and crystallization growth rates can be estimated.. AB - A molecular dynamics study has been conducted on an ...

Many uncommon gas flow phenomena in nanopores have been found by experiments. Besides that, another special characteristic of gas flow at nanopore is that gass number density shows uneven distribution. From the point of molecular motion, gass number density would affect its dynamic viscosity, so its very necessary to study whether the gass viscosity is uneven. Due to the gas densitys fluctuation usually takes place near the wall surface so the present paper focuses on the gass viscosity near the wall of nanopore. Our molecular dynamics simulation results indicate that the gass viscosity in the region near the wall surface isnt a constant and fluctuates greatly. The profiles of gass viscosity and gas number density coincide very well.. Copyright © 2013 by ASME ...

Kerford, M and Webb, RP (1999) Molecular Dynamics simulation of the desorption of molecules by energetic fullerene impacts on graphite and diamond surfaces In: 4th International Conference on Computer Simulation of Radiation Effects in Solids (COSIRES 98), 1998-09-15 - 1998-09-19, OKAYAMA, JAPAN. Full text not available from this repository ...

Ornithine cyclodeaminase (OCD) is an NAD+-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithines Cα-H group to the NAD+ cofactor with concomitant formation of a Cα=NH2+ Schiff base with a barrier of 90.6 kJ mol−1. Importantly, no water is observed within the active site during the MD simulations suitably positioned to hydrolyze the Cα=NH2+ intermediate to form the corresponding carbonyl. Instead, the reaction proceeds via a non-hydrolytic mechanism involving direct nucleophilic attack of the δ-amine at the Cα-position. This is then followed by cleavage and loss of the α-NH2 group to give

TY - JOUR. T1 - Molecular Dynamics Simulations of Wettability, Thermal Transport, and Interfacial Liquid Structuring at the Nanoscale in Polar Solid-Liquid Interfaces. AU - Gonzalez-Valle, C. Ulises. AU - Ramos-Alvarado, Bladimir. N1 - Funding Information: This research was supported in part by startup funds from The Pennsylvania State University. C.U.G.-V. was partially supported by the National Council on Science and Technology, Mexico, under the Scholarship Program 2018-000009-01EXTF-00048. Publisher Copyright: © PY - 2021/4/23. Y1 - 2021/4/23. N2 - Engineering nano- and microscale systems for water filtration, drug delivery, and biosensing is enabled by the intrinsic interactions of ionic compounds in aqueous environments and limited by our understanding of these polar solid-liquid interfaces. Particularly, the fundamental understanding of the electrostatic properties of the inner pore surface of alumina nanoporous membranes could lead to performance enhancement for evaporation and ...

TY - JOUR. T1 - Interfacial structures and vibrational spectra at liquid/liquid boundaries. T2 - Molecular dynamics study of water/carbon tetrachloride and water/1,2- dichloroethane interfaces. AU - Ishiyama, Tatsuya. AU - Sato, Yuji. AU - Morita, Akihiro. PY - 2012/10/11. Y1 - 2012/10/11. N2 - Flexible and polarizable molecular dynamics simulations are carried out to elucidate the structure and vibrational sum frequency generation (SFG) spectra of two water/organic liquid interfaces: water/carbon tetrachloride (CCl 4) and water/1,2-dichloroethane (DCE). Preceding experimental spectra by Richmond and co-workers have shown quite contrasting features of the two SFG spectra. The former spectrum is analogous with that of water/vapor interface with two-band structure, while the latter is structureless without feature of the dangling OH bond. The present calculations well reproduced these experimental features, though the orientational structure of interfacial water is found to be qualitatively ...

TY - JOUR. T1 - A molecular dynamics study of guest-host hydrogen bonding in alcohol clathrate hydrates. AU - Hiratsuka, Masaki. AU - Ohmura, Ryo. AU - Sum, Amadeu K.. AU - Alavi, Saman. AU - Yasuoka, Kenji. PY - 2015/5/21. Y1 - 2015/5/21. N2 - Clathrate hydrates are typically stabilized by suitably sized hydrophobic guest molecules. However, it has been experimentally reported that isomers of amyl-alcohol C5H11OH can be enclosed into the 51264 cages in structure II (sII) clathrate hydrates, even though the effective radii of the molecules are larger than the van der Waals radii of the cages. To reveal the mechanism of the anomalous enclathration of hydrophilic molecules, we performed ab initio and classical molecular dynamics simulations (MD) and analyzed the structure and dynamics of a guest-host hydrogen bond for sII 3-methyl-1-butanol and structure H (sH) 2-methyl-2-butanol clathrate hydrates. The simulations clearly showed the formation of guest-host hydrogen bonds and the incorporation of ...

Polyunsaturated phospholipids are known to be important with regard to the biological functions of essential fatty acids, for example, involving neural tissues such as the brain and retina. Here we have employed two complementary structural methods for the study of polyunsaturated bilayer lipids, viz. deuterium ((2)H) NMR spectroscopy and molecular dynamics (MD) computer simulations. Our research constitutes one of the first applications of all-atom MD simulations to polyunsaturated lipids containing docosahexaenoic acid (DHA; 22:6 cis-Delta(4,7,10,13,16,19)). Structural features of the highly unsaturated, mixed-chain phospholipid, 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC), have been studied in the liquid-crystalline (L(alpha)) state and compared to the less unsaturated homolog, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The (2)H NMR spectra of polyunsaturated bilayers are dramatically different from those of less unsaturated phospholipid bilayers. We show ...

The tau protein, whose aggregates are involved in Alzheimers disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition

Lipid peroxidation is a major deleterious effect caused by oxidative stress. It is involved in various diseases such as atherosclerosis, rheumatoid arthritis and neurodegenerative diseases. In order to inhibit lipid peroxidation, antioxidants must efficiently scavenge free radicals and penetrate inside biological membranes. Lipocarbazole has recently been shown to be a powerful antioxidant in solution. Here, we show its powerful capacity as lipid peroxidation inhibitor. Its mechanism of action is rationalized based on molecular dynamics simulations on a biomembrane model, quantum calculations and experimental evaluation. The role of the lipocarbazole side chain is particularly highlighted as a critical chemical feature responsible for its antioxidant activity.

Supercomputer simulations at the Department of Energys Oak Ridge National Laboratory are helping scientists unravel how nucleic acids could have contributed to the origins of life.. A research team led by Jeremy Smith, who directs ORNLs Center for Molecular Biophysics and holds a Governors Chair at University of Tennessee, used molecular dynamics simulation to probe an organic chemical reaction that may have been important in the evolution of ribonucleic acids, or RNA, into early life forms.. Certain types of RNA called ribozymes are capable of both storing genetic information and catalyzing chemical reactions - two necessary features in the formation of life. The research team looked at a lab-grown ribozyme that catalyzes the Diels-Alder reaction, which has broad applications in organic chemistry.. Life means making molecules that reproduce themselves, and it requires molecules and are sufficiently complex to do so, Smith said. If a ribozyme like the Diels-Alderase is capable of doing ...

Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4), and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO), which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD) simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation), a glycine

In this paper, we first investigate mechanisms of nanotube-based co-axial oscillators, shown in Figure 1, based on molecular dynamics simulation. We mainly study the interlayer friction between the outer tube and the inner tube when the oscillators are at finite temperatures. Based on our studies, we propose to design a nanoelectromechanical oscillator system, which can be utilized as memory cells. In addition, we propose the first numerical study of nanotube-based resonant oscillators, shown in Figure 2, via a new multiscale method. Temperature effects are also investigated.

ACM, the Association for Computing Machinery, named a nine-member team, drawn from Chinese and American institutions, recipients of the 2020 ACM Gordon Bell Prize for their project, Pushing the limit of molecular dynamics with ab initio accuracy to 100 million atoms with machine learning.

TY - JOUR. T1 - Impact of plasticity and flexibility on docking results for cytochrome P450 2D6: a combined approach of molecular dynamics and ligand docking. AU - Hritz, J.. AU - de Ruiter, A.. AU - Oostenbrink, C.. PY - 2008. Y1 - 2008. N2 - Cytochrome P450s (CYPs) exhibit a large plasticity and flexibility in the active site allowing for the binding of a large variety of substrates. The impact of plasticity and flexibility on ligand binding is investigated by docking 65 known CYP2D6 substrates to an ensemble of 2500 protein structures. The ensemble was generated by molecular dynamics simulations of CYP2D6 in complex with five representative substrates. The effect of induced fit, the conformation of Phe483, and thermal motion on the accuracy of site of metabolism (SOM) predictions is analyzed. For future predictions, the three most essential CYP2D6 structures were selected which are suitable for different kinds of ligands. We have developed a binary decision tree to decide which protein ...

A direct molecular dynamics simulation of the THz spectrum of a molecular crystal is presented. A time-dependent electric field is added to a molecular dynamics simulation of a crystal slab. The absorption spectrum is composed from the energy dissipated calculated from a series of applied pulses characterized by a carrier frequency. The spectrum of crystalline cyclotrimethylenetrinitramine (RDX) and triacetone triperoxide (TATP) were simulated with the ReaxFF force field. The proposed direct method avoids the linear response and harmonic approximations. A multidimensional extension of the spectroscopy is suggested and simulated based on the nonlinear response to a single polarized pulse of radiation in the perpendicular polarization direction. ...

TY - JOUR. T1 - Impact of cholesterol on voids in phospholipid membranes. AU - Falck, E.. AU - Patra, M.. AU - Karttunen, M.E.J.. AU - Hyvönen, M.T.. AU - Vattulainen, I.. PY - 2004. Y1 - 2004. N2 - Free volume pockets or voids are important to many biological processes in cell membranes. Free volume fluctuations are a prerequisite for diffusion of lipids and other macromolecules in lipid bilayers. Permeation of small solutes across a membrane, as well as diffusion of solutes in the membrane interior are further examples of phenomena where voids and their properties play a central role. Cholesterol has been suggested to change the structure and function of membranes by altering their free volume properties. We study the effect of cholesterol on the properties of voids in dipalmitoylphosphatidylcholine (DPPC) bilayers by means of atomistic molecular dynamics simulations. We find that an increasing cholesterol concentration reduces the total amount of free volume in a bilayer. The effect of ...

TY - JOUR. T1 - A multiscale simulation approach to modelling drug-protein binding kinetics. AU - Haldar, Susanta. AU - Comitani, Federico. AU - Saladino, Giorgio. AU - Woods, Christopher. AU - Van der Kamp, Marc. AU - Mulholland, Adrian. AU - Gervasio, Francesco Luigi. PY - 2018/9/13. Y1 - 2018/9/13. N2 - Drug-target binding kinetics has recently emerged as a sometimes critical determinant of in vivo efficacy and toxicity. Its rational optimization to improve potency or reduce side effects of drugs is, however, extremely difficult. Molecular simulations can play a crucial role in identifying features and properties of small ligands and their protein targets affecting the binding kinetics, but significant challenges include the long time scales involved in (un)binding events and the limited accuracy of empirical atomistic force fields (lacking, e.g., changes in electronic polarization). In an effort to overcome these hurdles, we propose a method that combines state-of-the-art enhanced sampling ...

Hydration properties of graphene oxide (GO) are essential for most of its potential applications. In this work, we employ atomistic molecular dynamics simulations to investigate seven GO compositions with different levels of oxygenation. Two atomic charge models for GO are compared: (1, a simplified model) sp2 carb

The role of active-site residues in the dealkylation reaction in the PSCS diastereomer of 2-(3,3-dimethylbutyl)methylphosphonofluoridate (soman)-inhibited Torpedo californicaacetylcholinesterase (AChE) was investigated by full-scale molecular dynamics simulations using CHARMM: , 400ps equilibration was followed by 150-200ps production runs with the fully solvated tetracoordinate phosphonate adduct of the wild-type, Trp84Ala and Gly199Gln mutants of AChE. Parallel simulations were carried out with the tetrahedral intermediate formed between serine-200 Oγ of AChE and acetylcholine. We found that the NεH in histidine H+-440 is positioned to protonate the oxygen in choline and thus promote its departure. In contrast, NεH in histidine H+-440 is not aligned for a favourable proton transfer to the pinacolyl O to promote dealkylation, but electrostatic stabilization by histidine H+-440 of the developing anion on the phosphonate monoester occurs. Destabilizing interactions between residues and the ...

Numerous models and methods have been employed in the chemistry and physics literature to study the molecular self-assembly process. Some recent reports have described molecular dynamics simulations [5-10], density functional theory [11], kinetic Monte Carlo simulations [12], stochastic models [13], graph theory [14] and mean-field models [15], to name a few. However, the possibility of studying self-assembly by selective retrieval of target information as described above has not been considered in this literature. In fact, the need for such a study seems to be particularly acute for the case of molecular self-assembly. For example, while molecular dynamics simulations should eventually yield reliable statistics on island formation, the simulation times required for the entire state space to be sufficiently sampled are inaccessible with modern computational power. The enormous state space of typical molecular self-assembly models, therefore, provides a barrier to both data collection and data ...

β-N-Acetylhexosaminidase (GH20) from the filamentous fungus Talaromyces flavus, previously identified as a prominent enzyme in the biosynthesis of modified glycosides, lacks a high resolution three-dimensional structure so far. Despite of high sequence identity to previously reported Aspergillus oryzae and Penicilluim oxalicum β-N-acetylhexosaminidases, this enzyme tolerates significantly better substrate modification. Understanding of key structural features, prediction of effective mutants and potential substrate characteristics prior to their synthesis are of general interest. Computational methods including homology modeling and molecular dynamics simulations were applied to shad light on the structure-activity relationship in the enzyme. Primary sequence analysis revealed some variable regions able to influence difference in substrate affinity of hexosaminidases. Moreover, docking in combination with consequent molecular dynamics simulations of C-6 modified glycosides enabled us to identify the

TY - CHAP. T1 - Review of the methods for local forces calculation in electrical apparatus. AU - Belahcen, Anouar. PY - 2002. Y1 - 2002. KW - coupled simulation. KW - electrical circuits. KW - electrical machines. KW - time consumption. KW - coupled simulation. KW - electrical circuits. KW - electrical machines. KW - time consumption. KW - coupled simulation. KW - electrical circuits. KW - electrical machines. KW - time consumption. M3 - Chapter. SP - 25. EP - 28. BT - Electromagnetic fields in electrical engineering ISEF01. A2 - A.Krawczyk, S.Wiak. PB - IOS PRESS. CY - Amsterdam, Alankomaat. ER - ...

Hybrid quantum/classical molecular dynamics simulations are used to compare the role of protein motion in the hydride transfer reaction catalyzed by Escherichia coli and Bacillus subtilis dihydrofolate reductase (DHFR). These two enzymes have 44% sequence identity, and the experimentally determined structures and hydride transfer rates are similar. The simulations indicate that the tertiary structures of both enzymes evolve in a similar manner during the hydride transfer reaction. In both enzymes, the donor-acceptor distance decreases to approximately 2.7 Angstroms at the transition state configurations to enable hydride transfer. Zero point energy and hydrogen tunneling effects are found to be significant for both enzymes. Covariance and rank correlation analyses of motions throughout the protein and ligands illustrate that E. coli and B. subtilis DHFR exhibit both similarities and differences in the equilibrium fluctuations and the conformational changes along the collective reaction coordinate for

Organic photovoltaic device efficiency is strongly influenced by the morphology of the active layer composed of conjugated polythiophenes (electron donors) and fullerene derivatives (electron acceptors). The goal of this thesis is to understand how molecular features affect the morphology and charge carrier dynamics in neat polythiophene and polythiophene-acceptor blends, using simulations and experiments. We use molecular dynamics simulations with our newly developed intermediate resolution model to study how oligothiophene (eg. poly(3-hexylthiophene), P3HT) and acceptor (eg. [6,6]-phenyl-C61-butyric acid methyl ester, PCBM) architecture and chemistry affect neat and blend morphology. Our coarse-grained model enables observation of molecular-level packing, e.g. the experimentally observed intercalation of acceptor molecules between oligomer side chains, as well as the transition from a disordered initial state to experimentally observed ordered morphologies. With this validated model, we study the

Marx, D and Hutter, J; Ab-initio Molecular Dynamics: Theory and Implementation In: Modern Methods and Algorithms of Quantum Chemistry, ed. by J. Grotendorst. Forschungszentrum Jülich, chap. 13, pp. 301-449.; link ...

The retinal response involves recoverin, a neuronal calcium-binding protein which binds onto the photoreceptor cell membrane. Although an approximate binding mechanism has been described, only the latest molecular dynamics simulations made it possible to elucidate in detail its individual stages and unravel the regulatory role of calcium.. Students Štěpán Timr, Roman Pleskot, Jan Kadlec, and others, together with their advisor Pavel Jungwirth shed light on the process in which the binding of two calcium ions to a recoverin molecule promotes the ejection of its hydrophobic myristoyl moiety. This moiety then serves to anchor recoverin to the cell membrane. The specific manner of recoverin binding prevents the action of rhodopsin kinase, the enzyme regulating the rhodopsin cycle. By suppressing the kinase, recoverin makes it ultimately possible for the retina to effectively adapt to changed illumination.. Molecular dynamics simulation has thus proven to be a unique tool to describe the molecular ...

The following is an incomplete list of [[models]] used in [[Computer simulation techniques , computer simulations]] of [[water]]: {{columns-list,3, ==A== *[[AMOEBA]] *[[ASP-S]] *[[ASP-W]] ==B== *[[Baranyai water model , Baranyai]] *[[BBL model of water , BBL]] *[[Bell-Lavis model of water , Bell-Lavis]] *[[Ben-Naim models of water ,Ben-Naim models ]] *[[BF]] *[[BJH]] *[[BK water models , BK3]] *[[BK water models , BKd1]] *[[BK water models , BKd2]] *[[BK water models , BKd3]] *[[Ben-Naim models of water#BNS model , BNS]] *[[Bol model of water , Bol]] *[[BSV]] ==C== *[[CC-pol]] *[[CF]] *[[CI]] *[[COS model of water,COS]] *[[COS model of water,COS/B2]] *[[COS model of water,COS/D2]] *[[COS model of water,COS/G2]] *[[COS model of water,COS/G3]] *[[CMP]] *[[CKL]] ==D== *[[Dahl and Andersen model of water,Dahl and Andersen]] *[[Dang97]] *[[DCF]] *[[DEC]] *[[DPP]] *[[DPP#DPP2,DPP2]] ==E== *[[E3B water model , E3B]] *[[E3B water model#E3B2 , E3B2]] *[[E3B water model#E3B3 , E3B3]] *[[ELBA water ...

High throughput methods accelerate the drug discovery, biomolecule detection and sequencing applications pipeline. Single molecule detection technique facilitates the implementation of high throughput methods by eliminating multi step evaluation. Label free high throughput biosensing methods pave way for studying nanoscale interactions of biological molecules in real-time. Nanopore based techniques have enabled the design of biosensors emerged as a new and rapidly developing label free real-time single molecule sensing technique. Biological nanopores typically realised using pore forming proteins, such as MspA porin and alpha hemolysin, are generally inserted into a lipid bilayer. These are great for sensitivity, but the proteins are difficult to handle. To mimic this biological nanopore, we have taken help from top-down and bottom-up nanotechnology to fabricate a bilayer nanopore. Scaffolded DNA origami is also a novel and unique method to fabricate tailor-made nanostructures with wide range of ...

To date, the fundamental details of the molecular structural changes and associated mechanisms, which take place during the formation of aluminosilicate geopolymer gels, have remained largely elusive. Here, density functional theory-based coarse-grained Monte Carlo modeling, a multiscale simulation technique, is used to simulate the geopolymerization reaction and to determine the molecular mechanisms controlling this process. Silica supplied by the alkaline solution plays a significant role in enhancing the dissolution of the solid aluminosilicate precursor (metakaolin, in this case) and the polymerization of the gel. In the reaction between NaOH and metakaolin, in the absence of initially dissolved silica, the solid precursor completely dissolves and the aluminosilicate gel forms via the percolation of small aluminosilicate clusters. On the other hand, in the presence of dissolved silicate, the metakaolin only partially dissolves, as the aluminosilicate gel precipitates on the surfaces of the ...

Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a ...

TY - CHAP. T1 - Tracer diffusion in n-alkene liquids and polymers. A non-equilibrium molecular dynamics study. AU - van der Vegt, N.F.A.. AU - Briels, Willem J.. AU - Wessling, Matthias. AU - Strathmann, H.. PY - 1997. Y1 - 1997. KW - IR-12848. KW - METIS-107029. M3 - Chapter. SN - 90-365-09726. SP - 76. EP - 76. BT - Proceedings in Book of Abstracts Euromembrane 97, third international symposium Progress in Membrane, Science and Technology. PB - European Society for Membrane Science and Technology. CY - Enschede. ER - ...

Somatostatin receptor 2 (SSTR2) is a G-protein coupled receptor (GPCR) that controls numerous cellular processes including cell-to-cell signaling. In this study, we report how the lipid and ligand molecules influence the conformational dynamics of the membrane-bound SSTR2. Molecular simulations of different holo and apoenzyme complexes of SSTR2 in the presence and absence of a lipid bilayer were performed, observed, and correlated with previously reported studies. We identified the important SSTR2 residues that take part in the formation of the SSTR2-ligand complex. On analyzing the molecular simulation trajectories, we identified that the residue D3.32 is crucial in determining the bioactive conformation of SSTR2 ligands in the binding site. Based on the results, we suggest that designing a novel SSTR2 ligand with an H-bond donor group at the R1 position, and hydrophobic groups at R2 and R3 might have higher activity and SSTR2-selectivity. We analyzed the simulated systems to identify other important

Na(+)/H(+) antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the conformational stability and lipid-binding properties of the Na(+)/H(+) exchanger NapA from Thermus thermophilus and compare this to the prototypical antiporter NhaA from Escherichia coli and the human homologue NHA2. We find that NapA and NHA2, but not NhaA, form stable dimers and do not selectively retain membrane lipids. By comparing wild-type NapA with engineered variants, we show that the unfolding of the protein in the gas phase involves the disruption of inter-domain contacts. Lipids around the domain interface protect the native fold in the gas phase by mediating contacts between the mobile protein segments. We speculate that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate

norelated *研究室教員 [#p5dc9aa5] -教授 高柳 敏幸 *発表論文 [#s346800c] +Molecular dynamics simulations of small glycine-(H2O)&subsc{n}; (n = 2-7) clusters on semiempirical PM6 potential energy surfaces, T. Takayanagi, T. Yoshikawa, A. Kakizaki, M. Shiga, and M. Tachikawa, J. Mol. Struct. (THEOCHEM), 869, 29-36 (2008). +Molecular dynamics simulations of small glycine-(H&subsc{2};O)&subsc{n}; (n = 2-7) clusters on semiempirical PM6 potential energy surfaces, T. Takayanagi, T. Yoshikawa, A. Kakizaki, M. Shiga, and M. Tachikawa, J. Mol. Struct. (THEOCHEM), 869, 29-36 (2008). +Path-integral molecular dynamics simulations of BeO embedded in helium clusters: Formation of the stable HeBeO complex, H. Motegi, A. Kakizaki, T. Takayanagi, Y. Taketsugu, T. Taketsugu, and M. Shiga, Chem. Phys. 354, 38-43 (2008). +Linkage isomerism of pentaammine(dimethylsulfoxide)ruthenium(II/III) complexes: a thoretical study, M. Kato, T. Takayanagi, T. Fujihara, and A. Nagasawa, Inorg. Chimi. Acta, ...

We use all-atom MD simulations, combined with patch-clamp electrophysiology and time-resolved fluorescence spectroscopy, to investigate functional dynamics of neurotransmitter transporters and Cl- channels. We developed kinetic state models to explain the functional coupling of secondary active glutamate transport and channel-like anion conduction in EAAT glutamate transporters (1-3), and advanced noise analysis techniques to measure unitary properties of transporter-associated channels (4). Using stopped-flow fluorescence recordings, we identified an induced-fit substrate binding mechanism in EAATs (4). The prokaryotic EAAT homolog GltPh is the founding member of the group of transporters with an elevator transport mechanism, and we used essential dynamics sampling to simulate the inward-outward transition path (5). We identified the Cl- permeation pathway and Cl- conduction mechanism in EAATs (5,6) using Computational Electrophysiology, a simulation technique for all-atom MD simulations of ...

Catalytic cracking of alkenes takes place at elevated temperatures in the order of 773-833 K. In this work, the nature of the reactive intermediates at typical reaction conditions is studied in H-ZSM-5 using a complementary set of modeling tools. Ab initio static and molecular dynamics simulations are performed on different C4single bond C5 alkene cracking intermediates to identify the reactive species in terms of temperature. At 323 K, the prevalent intermediates are linear alkoxides, alkene π-complexes and tertiary carbenium ions. At a typical cracking temperature of 773 K, however, both secondary and tertiary alkoxides are unlikely to exist in the zeolite channels. Instead, more stable carbenium ion intermediates are found. Branched tertiary carbenium ions are very stable, while linear carbenium ions are predicted to be metastable at high temperature. Our findings confirm that carbenium ions, rather than alkoxides, are reactive intermediates in catalytic alkene cracking at 773 K. ...