Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Tandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Models, Theoretical: Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Child Development: The continuous sequential physiological and psychological maturing of an individual from birth up to but not including ADOLESCENCE.Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Methods: A series of steps taken in order to conduct research.Monte Carlo Method: In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993)Quantum Theory: The theory that the radiation and absorption of energy take place in definite quantities called quanta (E) which vary in size and are defined by the equation E=hv in which h is Planck's constant and v is the frequency of the radiation.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Molecular Dynamics Simulation: A computer simulation developed to study the motion of molecules over a period of time.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)Medical Informatics: The field of information science concerned with the analysis and dissemination of medical data through the application of computers to various aspects of health care and medicine.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Biomedical Technology: The application of technology to the solution of medical problems.Skin Neoplasms: Tumors or cancer of the SKIN.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Leprosy: A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid.Mycobacterium leprae: A species of gram-positive, aerobic bacteria that causes LEPROSY in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Employment: The state of being engaged in an activity or service for wages or salary.Bioethics: A branch of applied ethics that studies the value implications of practices and developments in life sciences, medicine, and health care.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Biochemistry: The study of the composition, chemical structures, and chemical reactions of living things.Chlamydiales: An order of obligately intracellular, gram-negative bacteria that have the chlamydia-like developmental cycle of replication. This is a two-stage cycle that includes a metabolically inactive infectious form, and a vegetative form that replicates by binary fission. Members of Chlamydiales are disseminated by aerosol or by contact. There are at least six recognized families: CHLAMYDIACEAE, Criblamydiaceae, Parachlamydiaceae, Rhabdochlamydia, Simkaniaceae, and Waddliaceae.Nanotechnology: The development and use of techniques to study physical phenomena and construct structures in the nanoscale size range or smaller.Bays: An area of water mostly surrounded by land, usually smaller than a gulf, and affording access to the sea.Posters as Topic: Single or multi-sheet notices made to attract attention to events, activities, causes, goods, or services. They are for display, usually in a public place and are chiefly pictorial.Nanostructures: Materials which have structured components with at least one dimension in the range of 1 to 100 nanometers. These include NANOCOMPOSITES; NANOPARTICLES; NANOTUBES; and NANOWIRES.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

Evidence on the conformation of HeLa-cell 5.8S ribosomal ribonucleic acid from the reaction of specific cytidine residues with sodium bisulphite. (1/64258)

The reaction of HeLa-cell 5.8S rRNA with NaHSO3 under conditions in which exposed cytidine residues are deaminated to uridine was studied. It was possible to estimate the reactivities of most of the 46 cytidine residues in the nucleotide sequence by comparing 'fingerprints' of the bisulphite-treated RNA with those of untreated RNA. The findings were consistent with the main features of the secondary-structure model for mammalian 5.85S rRNA proposed by Nazar, Sitz, & Busch [J. Biol. Chem (1975) 250, 8591--8597]. Five out of six regions that are depicted in the model as single-stranded loops contain cytidine residues that are reactive towards bisulphite at 25 degrees C (the other loop contains no cytidine). The cytidine residue nearest to the 3'-terminus is also reactive. Several cytidines residues that are internally located within proposed double-helical regions show little or no reactivity towards bisulphite, but the cytidine residues of several C.G pairs at the ends of helical regions show some reactivity, and one of the proposed loops appears to contain six nucleotides, rather than the minimum of four suggested by the primary structure. Two cytidine residues that are thought to be 'looped out' by small helix imperfections also show some reactivity.  (+info)

Endocytosis: EH domains lend a hand. (2/64258)

A number of proteins that have been implicated in endocytosis feature a conserved protein-interaction module known as an EH domain. The three-dimensional structure of an EH domain has recently been solved, and is likely to presage significant advances in understanding molecular mechanisms of endocytosis.  (+info)

Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. (3/64258)

The crystal structure of profactor D, determined at 2.1 A resolution with an Rfree and an R-factor of 25.1 and 20.4%, respectively, displays highly flexible or disordered conformation for five regions: N-22, 71-76, 143-152, 187-193 and 215-223. A comparison with the structure of its mature serine protease, complement factor D, revealed major conformational changes in the similar regions. Comparisons with the zymogen-active enzyme pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar distribution of the flexible regions. However, profactor D is the most flexible of the four, and its mature enzyme displays inactive, self-inhibited active site conformation. Examination of the surface properties of the N-terminus-binding pocket indicates that Ile16 may play the initial positioning role for the N-terminus, and Leu17 probably also helps in inducing the required conformational changes. This process, perhaps shared by most chymotrypsinogen-like zymogens, is followed by a factor D-unique step, the re-orientation of an external Arg218 to an internal position for salt-bridging with Asp189, leading to the generation of the self-inhibited factor D.  (+info)

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (4/64258)

Amyloid fibrils are assemblies of misfolded proteins and are associated with pathological conditions such as Alzheimer's disease and the spongiform encephalopathies. In the amyloid diseases, a diverse group of normally soluble proteins self-assemble to form insoluble fibrils. X-ray fibre diffraction studies have shown that the protofilament cores of fibrils formed from the various proteins all contain a cross-beta-scaffold, with beta-strands perpendicular and beta-sheets parallel to the fibre axis. We have determined the threedimensional structure of an amyloid fibril, formed by the SH3 domain of phosphatidylinositol-3'-kinase, using cryo-electron microscopy and image processing at 25 A resolution. The structure is a double helix of two protofilament pairs wound around a hollow core, with a helical crossover repeat of approximately 600 A and an axial subunit repeat of approximately 27 A. The native SH3 domain is too compact to fit into the fibril density, and must unfold to adopt a longer, thinner shape in the amyloid form. The 20x40-A protofilaments can only accommodate one pair of flat beta-sheets stacked against each other, with very little inter-strand twist. We propose a model for the polypeptide packing as a basis for understanding the structure of amyloid fibrils in general.  (+info)

Structural basis for the specificity of the initiation of HIV-1 reverse transcription. (5/64258)

Initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription requires specific recognition of the viral genome, tRNA3Lys, which acts as primer, and reverse transcriptase (RT). The specificity of this ternary complex is mediated by intricate interactions between HIV-1 RNA and tRNA3Lys, but remains poorly understood at the three-dimensional level. We used chemical probing to gain insight into the three-dimensional structure of the viral RNA-tRNA3Lys complex, and enzymatic footprinting to delineate regions interacting with RT. These and previous experimental data were used to derive a three-dimensional model of the initiation complex. The viral RNA and tRNA3Lys form a compact structure in which the two RNAs fold into distinct structural domains. The extended interactions between these molecules are not directly recognized by RT. Rather, they favor RT binding by preventing steric clashes between the nucleic acids and the polymerase and inducing a viral RNA-tRNA3Lys conformation which fits perfectly into the nucleic acid binding cleft of RT. Recognition of the 3' end of tRNA3Lys and of the first template nucleotides by RT is favored by a kink in the template strand promoted by the short junctions present in the previously established secondary structure.  (+info)

The highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes. (6/64258)

Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a beta-hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins of the Ets proto-oncogene family to bind a composite DNA site that is essential for efficient transcription of the early-B-cell-specific mb-1 promoter. Here, evidence is provided for specific interactions between Ets-1 and the amino-terminal subdomains of Pax proteins. By tethering deletion fragments of Pax-5 to a heterologous DNA-binding domain, we show that 73 amino acids (amino acids 12 to 84) of its amino-terminal subdomain can recruit the ETS domain of Ets-1 to bind the composite site. Furthermore, an amino acid (Gln22) within the highly conserved beta-hairpin motif of Pax-5 is essential for efficient recruitment of Ets-1. The ability to recruit Ets proteins to bind DNA is a shared property of Pax proteins, as demonstrated by cooperative DNA binding of Ets-1 with sequences derived from the paired domains of Pax-2 and Pax-3. The strict conservation of sequences required for recruitment of Ets proteins suggests that Pax-Ets interactions are important for regulating transcription in diverse tissues during cellular differentiation.  (+info)

Identification of DNA polymorphisms associated with the V type alpha1-antitrypsin gene. (7/64258)

alpha1-Antitrypsin (alpha1-AT) is a highly polymorphic protein. The V allele of alpha1-AT has been shown to be associated with focal glomerulosclerosis (FGS) in Negroid and mixed race South African patients. To identify mutations and polymorphisms in the gene for the V allele of alpha1-AT in five South African patients with FGS nephrotic syndrome DNA sequence analysis and restriction fragment length polymorphisms of the coding exons were carried out. Four of the patients were heterozygous for the BstEII RFLP in exon III [M1(Val213)(Ala213)] and one patient was a M1(Ala213) homozygote. The mutation for the V allele was identified in exon II as Gly-148 (GGG)-->Arg (AGG) and in all patients was associated with a silent mutation at position 158 (AAC-->AAT). The patient who was homozygous for (Ala213) also had a silent mutation at position 256 in exon III (GAT-->GAC) which was not present in any of the other four patients. Although the V allele of alpha1-AT is not associated with severe plasma deficiency, it may be in linkage disequilibrium with other genes on chromosome 14 that predispose to FGS. Furthermore, the associated silent mutation at position 158 and the Ala213 polymorphism are of interest, as these could represent an evolutionary intermediate between the M1(Ala213) and M1(Val213) subtypes.  (+info)

Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. (8/64258)

Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.  (+info)

  • Written for the highly successful Methods in Molecular Biology series, chapters include thorough introductions, step-by-step instructions, and notes on troubleshooting and avoiding common pitfalls. (
  • A total of 20 university credits (hp) in Biotechnology or Molecular Biology. (
  • Cancer Commons puts the patient at the front end of a remarkable experiment in 'translational medicine' - one in which basic molecular biology, computational methods and a network of experts and institutions collaborate to work out personalized medical solutions," said Donald Kennedy, Ph.D., Editor-in-Chief, Science (2000-2008). (
  • The discovery of numerous non-coding RNAs has dramatically changed our understanding of cell biology, especially the pathophysiology of breast cancer and we aim to investigate their role in breast cancer development using 3D models. (
  • The Ahmed and Coutts groups are within the world-leading REF2014 Biomedical Sciences Research Centre and has experience of a range of molecular cell biology techniques, including mammalian cell culture, 3D cultures, expression analysis, immunofluorescence, real time QPCR and Western blot analysis. (
  • Applicants should hold, or be expected to hold, an UK Master's degree (or UK equivalent according to NARIC) with a minimum of a commendation, and/or a UK 1stClass / 2.1 Bachelor's Honour's Degree (or UK equivalent according to NARIC) in Cell Biology, Biochemistry, Molecular Biology, or a related Biosciences related subject. (
  • To see more employment opportunities with European Molecular Biology Laboratory (EMBL), please click here . (
  • Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. (
  • It is proved that the proposed SSCM strategy can remarkably improve the external prediction ability of QSAR models by employing two different datasets. (
  • C. Hansch and T.E. Klein , QSAR and Molecular Graphics in Evaluation of Enzyme-Ligand Interactions. (
  • Docking is among a number of structural bioinformatics strategies trying to understand molecular recognition, both to understand structure to function relationships in macromolecules, and to derive tools useful in fields like drug design. (
  • The main focus of our research is the development and optimization for High-Performing-Computing (HPC) of computational methodology for the structural and energetic characterization of protein interactions at molecular level. (
  • From the very early stages of structural studies of DNA by X-ray diffraction and biochemical means, molecular models such as the Watson-Crick nucleic acid double helix model were successfully employed to solve the 'puzzle' of DNA structure, and also find how the latter relates to its key functions in living cells. (
  • Structural information is generated from X-ray diffraction studies of oriented DNA fibers with the help of molecular models of DNA that are combined with crystallographic and mathematical analysis of the X-ray patterns. (
  • To broaden the scope of this model, we propose the symmetry-adapted orbital model, which explicitly takes into account the level splittings of the electronic orbitals due to lower structural symmetries. (
  • 2) Draw Lewis structures and/or structural formulas of selected models. (
  • However, structural models coupled with biophysical and machine learning methods may be able to predict sequences that, when mutated, would be associated with more severe forms of OI. (
  • To build appropriate structural models, we have applied a high throughput molecular dynamic approach. (
  • Our models revealed structural differences that occur with different substituting amino acids. (
  • In this study, we applied a molecular dynamics method to the analysis of the structural consequences of 57 disease-associated mutations in the α1(I) chain of type I collagen. (
  • Moreover, the traditional approach uses mathematical formulas or algorithms that are run sequentially, refining the structural details of the model with each separate algorithm a method that has been revolutionized by personal computing, but still requires labor-intensive human intervention for error correction. (
  • A new method developed by scientists on the Florida campus of The Scripps Research Institute (TSRI) takes another tack entirely, combining existing formulas in a kind of algorithmic stew to gain a better picture of molecular structural diversity that is then used to eliminate errors and improve the final model. (
  • Models encompass a wide range of degrees of precision and engineering: some models such as J.D. Bernal's water are conceptual, while the macromodels of Pauling and Crick and Watson were created with much greater precision. (
  • MSMs for molecular kinetics are conceptually similar to our road-map example but instead of intersections, the states now correspond to basins in the free energy landscape governing the dynamics of the molecule. (
  • Nettles and his colleagues measured the improvement in the models by what is known as the R-factor, which measures the similarity between the actual structure of the molecule and the experimental model in other words, just how closely the refined structure model can predict the factual data. (
  • The monograph discusses models of synthetic protocells, which are cell-like structures obtained from non-living matter endowed with some rudimentary kind of metabolism and genetics, but much simpler than biological cells. (
  • The Lung Cancer model supplies doctors and their patients with a clear, high‐level guide to how tumor genetics can be leveraged to inform treatment decisions. (
  • Plant Molecular Genetics and Center for Legume Research, The University of Tennessee, Knoxville, TN 37901-1071 U.S.A. (
  • For this reason, the Bayesian least absolute shrinkage and selection operator (LASSO) (BL) appears to be an interesting approach for fitting marker effects in a regression model. (
  • Regressors include linear models (Bayesian ridge regression (BR) and linear regression with elastic net regularization (EN)), random forest (RF), kernel ridge regression (KRR) and two types of neural networks, graph convolutions (GC) and gated graph networks (GG). (
  • d) Distribution of root-mean-square deviation of the non-hydrogen atoms in binding site residues (RMSD bs ) between a comparative model and a target X-ray structure. (
  • John Dalton represented compounds as aggregations of circular atoms, and although Johann Josef Loschmidt did not create physical models, his diagrams based on circles are two-dimensional analogues of later models. (
  • The concept of the chemical bond as a direct link between atoms can be modelled by linking balls (atoms) with sticks/rods (bonds). (
  • The reason for the difference between graphite and diamond lies in their molecular structure--how the carbon atoms are joined together. (
  • The models can be completed in any order, this helps free up the materials so that not all students are waiting to use the Carbon or Sodium atoms. (
  • This course is an extension of the course Molecular Modeling BB2280, and the aim is that the student should use the theoretical knowledge of BB2280 to solve a real chemical or biochemical problem. (
  • Matt's expertise is specifically in the reconciliation of experimental and theoretical data to produce models that are indicative of actual, lab-scale behaviours and outcomes. (
  • Although such initial studies of DNA structures with the help of molecular models were essentially static, their consequences for explaining the in vivo functions of DNA were significant in the areas of protein biosynthesis and the quasi-universality of the genetic code. (
  • A molecular subtype of melanoma is loosely defined as those tumors containing the same set of molecular (primarily genetic) defect(s) and their associated pathways. (
  • Recent developments in our understanding of the molecular drivers of this disease have led to a new generation of targeted therapies that are proving effective in patients whose tumors harbor certain genetic defects. (
  • The information set now available for predicting genetic values may include, in addition to phenotypic records, a pedigree, molecular markers, or both. (
  • Computational tools for analyzing the molecular consequences of genetic variation are of current interest because they have the potential to characterize the molecular pathogenesis for disease ( 1 - 3 ). (
  • The model legume Lotus japonicus was demonstrated to be amenable to classical and molecular genetic analysis, providing the basis for the genetic dissection of the plant processes underlying nodulation and nitrogen fixation. (
  • The results demonstrate that (i) Lotus japonicus is amenable to diploid genetic analysis, (ii) morphological and molecular markers segregate in true diploid fashion, (iii) molecular polymorphisms can be obtained at a reasonable frequency between the related Gifu and Funakura lines, and iv) the possibility exists for map-based cloning, marker assisted selection and mapping of symbiotic mutations through a genetic and molecular map. (
  • Here we describe and study a stochastic, individual-based, explicit genetic model tailored for this palms system. (
  • Different protocell "architectures" have been proposed and high-level abstract models like those that are presented in this book are particularly relevant to gain a better understanding of the different properites. (
  • An advantage of explicitly regressing phenotypes on marker covariates is that the model can produce information about genomic regions that may affect the trait of interest. (
  • Molecular motion at finite (non-zero) temperature is explicitly accounted for at non-quantized level via Newton's equations. (
  • These findings indicate that ML models could be more accurate than DFT if explicitly electron correlated quantum (or experimental) data was provided. (
  • When the empirical knowledge about the systematic difference in selective pressures is available, regarding the fluctuating environment, it is possible to explicitly model condition-specific amino acid fitness modulations. (
  • Molecular structures and properties at hybrid density functional theory (DFT) level of theory used for training and testing come from the QM9 database [Ramakrishnan et al, Scientific Data 1 140022 (2014)] and include dipole moment, polarizability, HOMO/LUMO energies and gap, electronic spatial extent, zero point vibrational energy, enthalpies and free energies of atomization, heat capacity and the highest fundamental vibrational frequency. (
  • Even for single models, the models are significantly more enriching than the template structure if the template is paralogous and shares more than 25% sequence identity with the target. (
  • Enrichment curves for the holo X-ray structure (black line), the apo X-ray structure (blue line), the consensus enrichment for multiple models (red line), and random selection (dotted line). (
  • For 8 targets (6 enzymes, one of which is a kinase, and 2 hormone receptors), enrichment curves are plotted for the holo X-ray structure (dotted line), the consensus based on multiple models (black line), and each single model (brown lines). (
  • In an effort to understand the role of the linker histone in chromatin folding, its structure and location in the nucleosome has been studied by molecular modeling methods. (
  • The structure of the globular domain of the rat histone H1d, a highly conserved part of the linker histone, built by homology modeling methods, revealed a three-helical bundle fold that could be described as a helix-turn-helix variant with its characteristic properties of binding to DNA at the major groove. (
  • Coordinate systems: how to describe 3-D molecular structure. (
  • The first reports of a double helix molecular model of B-DNA structure were made by James Watson and Francis Crick in 1953. (
  • In this article, "molecular model" will primarily refer to systems containing more than one atom and where nuclear structure is neglected. (
  • The symmetrical arrangement of closely packed spheres informed theories of molecular structure in the late 1800s, and many theories of crystallography and solid state inorganic structure used collections of equal and unequal spheres to simulate packing and predict structure. (
  • Computer simulation and modeling have become powerful tools for understanding the structure and properties of a broad range of materials. (
  • Accordingly, a cluster will be stable when the number of valence electrons coincides with a closed-shell structure based on the jellium model. (
  • Molecular Modeling Techniques in Materials Science presents the background and tools for chemists and physicists to perform in-silico experiments to understand relationships between the properties of materials and the underlying atomic structure. (
  • How to Build a Model of the Molecular Structure of Graphite. (
  • To estimate the tree structure for a set of taxa, we typically use a statistical model for evolution and compute the maximum likelihood estimate. (
  • Computer model of the molecular structure of a crystal, used to demonstrate ideas on perspective. (
  • This interactive tutorial explores how sound waves exhibit anisotropic character as a function of grain structure when traveling through a wooden block, which serves as an excellent model for the behavior of light passing through anisotropic crystals. (
  • The success of this "blind" test increases our confidence in the overall correctness of our proposed alignment of the enzyme sequence with those of other proteases of known structure and constitutes a first step in the construction of a complete model of the viral protease domain. (
  • J. de Vlieg and W.F. van Gunsteren , Combined Procedures of Distance Geometry and Molecular Dynamics ~for Determining Protein Structure from NMR Data. (
  • The creation of mathematical models of molecular properties and behaviour is molecular modelling, and their graphical depiction is molecular graphics, but these topics are closely linked and each uses techniques from the others. (
  • Sustainable protocell populations have not yet been obtained experimentally and mathematical models are therefore extremely important to address key questions concerning their synthesis and behavior. (
  • Case studies and mathematical models of ecological speciation. (
  • We discuss patterns and time-scales of ecological speciation identified by our model, and we highlight important parameters and features that need to be studied empirically in order to provide information that can be used to improve the biological realism and power of mathematical models of ecological speciation. (
  • The MDMM consists of a set of "actionable" molecular subtypes and proposed practice guidelines for treating each subtype: which therapies (approved or experimental) should be considered and which are contraindicated. (
  • The model predictions of molecular uptake are in excellent agreement with these experimental measurements, for which the applied electric pulses collectively span nearly three orders of magnitude in pulse duration (50 ts -20 ms) and an order of magnitude in pulse magnitude (0.3 -3 kV/cm). (
  • This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. (
  • Molecular modelling is a powerful and versatile toolbox that complements experimental data and provides insights where direct observation is not currently possible. (
  • Molecular alterations of canalicular transport systems in experimental models of cholestasis: possible functional correlations. (
  • Canalicular excretion of bile salts and several non-bile acid organic anions is impaired in various experimental models of cholestasis. (
  • This article gives an overview on molecular alterations of canalicular transport systems in experimental models of cholestasis and discusses the potential implications of these changes for the pathophysiology of cholestasis. (
  • Christopher S. Anderson, Marta L. DeDiego, David J. Topham, and Juilee Thakar, "Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection," Computational and Mathematical Methods in Medicine , vol. 2016, Article ID 7686081, 11 pages, 2016. (
  • To clarify their roles, and possible cross-talk, we have built a logical model for the nine key signalling pathways recurrently used in metazoan development. (
  • Moreover, these models of Drosophila pathways could serve as scaffolds for more complicated models of orthologous mammalian pathways. (
  • Comprehensive model annotations and GINsim files are provided for each of the nine considered pathways. (
  • As one of our main research lines, we model enzymatic activity addressing not only the atomic (and electronic) detailed mechanism but also suggesting mutations for changes in activity, substrate specificity, etc. (
  • His main research interests, besides protocells, concern the dynamical modelling of Complex Systems, with applications to gene regulatory networks and cell differentiation, the analysis of their organization and the dynamical systems approach to Artificial Intelligence. (
  • Implemented using the logical modelling software GINsim , the resulting models qualitatively recapitulate the main characteristics of each pathway, in wild type as well as in various mutant situations ( e.g. loss-of-function or gain-of-function). (
  • By developing and applying molecular simulation techniques to efficiently investigate these processes we aim at addressing open questions in pharmaceutical manufacturing and functional materials design. (
  • These models constitute pluggable modules that can be used to assemble comprehensive models of complex developmental processes. (
  • Molecular processes in nature affect human health, the availability of resources and the Earth s climate. (
  • In October 2011, a project was initiated within the Fluids & Energy group to develop molecular-based computational tools for predicting fundamental physicochemical characteristics required for understanding and rational design of CO 2 separation processes and long-term CO 2 storage in geological formations. (
  • Recent years have seen an increasing demand for drug discovery and development processes to use more predictive, higher complexity, physiologically-relevant three-dimensional (3D) cell models which better mimic in vivo environments than simpler two-dimensional (2D) models. (
  • Due to recent advancements of computers and algorithms, one can treat fairly large macromolecular systems with BOMD and even include significant portion of the first solvation shell surrounding a large reacting complex in the molecular model. (
  • In the study, the scientists subjected more than 50 molecular structures to 256 distinct combinations of algorithms and refinement factors that eventually totaled more than 12,000 independent refinement runs. (
  • Some algorithms, if you combine them, tend to work better at producing a refined model, said Research Associate Jerome C. Nwachukwu, the first author of the study. (
  • MSL is a set of tools that supports a large variety of algorithms for the design, modeling, and analysis of macromolecules. (
  • We propose it as a common platform for the development of new molecular algorithms and to promote the distribution, sharing, and reutilization of computational methods. (
  • We show that these methods give insight into the underlying adsorption mechanisms of pure components in model DNCs and that the application of these methods can be extended to mixtures and used to develop design criteria for new materials with improved separations capabilities. (
  • The Debenedetti group is using state-of-the-art molecular modeling tools to gain insights into the mechanisms and rates of melting and formation of carbon dioxide and methane hydrates, as well as on their thermodynamic stability across broad ranges of temperature, pressure and salinity. (
  • As described by the jellium model, molecular orbitals generated by valence electrons in highly symmetric clusters have shapes just like atomic orbitals. (
  • The atomic and molecular orbital parts are represented by pastel/matte colored pieces and are color-coded according to their use. (
  • The pink and purple pear-shaped lobes and concave pi links represent the +ve and -ve signs of the wave functions Ψ of the lobes of atomic and molecular orbitals. (
  • MSL has a number of unique features, such as the ability of storing alternative atomic coordinates (for modeling) and multiple amino acid identities at the same backbone position (for design). (
  • the first of these, The Targeted Therapy Finder - Melanoma, leverages the MDMM to find treatments targeted to a patient's specific molecular profile. (
  • In providing financial support for this important open-science initiative, we are aiming to help physicians and patients understand the therapeutic options that best fit the patient's molecular profile, with the goal of delivering more effective, personalized care. (
  • Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. (
  • Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients. (
  • To better understand disease pathogenesis, we use a Drosophila fragile X model, based on loss of dfmr1 function, which displays several relevant phenotypes, including defects in the circadian output pathway, memory in the conditioned courtship and olfactory conditioning paradigms, social interaction (with peers and in naïve courtship) and neural development. (
  • Notably, the mGluR pathway has been shown to be misregulated in both mouse and fly models of FXS, and, importantly, treatment with mGluR inhibitors rescues memory and other phenotypes in both Drosophila and mammalian models of the disease. (
  • c) Distribution of N-DOPE statistical potential score for comparative models (black and red bars for models based on holo and apo templates, respectively) and target X-ray structures (empty blue bars). (
  • Conversely, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. (
  • In this thesis, we describe a quantitative, mechanistic model of electroporation and concomitant molecular transport that can be used for guiding and interpreting electroporation experiments and applications. (
  • I am interested in molecular modeling of Antigenic peptide of M Leprae and its interaction with T cell CD4+ with the MHCII complex .I have chosen an antigenic peptide of 12k obtained from field trials in India.Is there any other proven antigenic peptide of m-lepray?If so what is the amino acid sequence? (
  • In such clusters, the validity of the spherical jellium model decreases relatively due to the split and shift of the superatomic orbital levels. (
  • We suggest how to exploit comparative models for molecular screens, based on docking against a wide range of crystallographic structures and comparative models with known ligands. (
  • To account for the variation in the ligand-binding pocket as it binds different ligands, we calculate "consensus" enrichment by ranking each library compound by its best docking score against all available comparative models and/or modeling templates. (
  • Various representations from the literature have been studied (Coulomb matrix, bag of bonds, BAML and ECFP4, molecular graphs (MG)), as well as newly developed distribution based variants including histograms of distances (HD), and angles (HDA/MARAD), and dihedrals (HDAD). (
  • Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains today's best protocols for classifying tumors into response categories and for customizing therapy to individuals. (
  • Two orders of magnitude more protein sequences can be modeled by comparative modeling than have been determined by X-ray crystallography and NMR spectroscopy. (
  • Investigators have nevertheless been cautious about using comparative models for ligand discovery because of concerns about model errors. (
  • a, b) Scatter plots of the difference between the enrichments for a comparative model and the corresponding template ( Δ log AUC m-t = log AUC mod el - log AUC template ) versus the target-template sequence identity. (