• Functional and structural characterization of human adrenoleukodystrophy protein (ALDP). (elifesciences.org)
  • Characterization and classification of protein-protein interactions would allow us to organize information in protein-protein interaction networks, to make predictions on their function, as well as to facilitate drug design targeted at interfering with those disease-associated protein-protein interactions. (biomedcentral.com)
  • Systematic characterization of the protein interaction network and protein complexes in Saccharomyces cerevisiae using tandem affinity purification and mass spectrometry. (leibniz-fli.de)
  • We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. (elifesciences.org)
  • Therefore computational prediction of protein features from their sequence is often used for designing strategies for experimental characterization of proteins and is also important for genome annotation and drug target identification [ 4 , 5 ]. (biomedcentral.com)
  • These interactions between proteins are dependent on highly specific binding between proteins to ensure efficient electron transfer. (wikipedia.org)
  • At multiple time points during evolution, new or modified proteins - and consequently new potential interactions between proteins - have emerged. (elifesciences.org)
  • All this information enables the creation of large protein interaction networks - similar to metabolic or genetic/epigenetic networks - that empower the current knowledge on biochemical cascades and molecular etiology of disease, as well as the discovery of putative protein targets of therapeutic interest. (wikipedia.org)
  • The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. (mdpi.com)
  • Protein-protein interaction inhibition (2P2I): fewer and fewer undruggable targets. (leibniz-fli.de)
  • Post-translational modifications of proteins provide targets for T cells that have not been subject to central tolerance. (bmj.com)
  • This study provides the first evidence that homocitrullinated proteins in tumors can also be targets for CD8 T-cell responses. (bmj.com)
  • This research suggests that post-translational modification of proteins provide efficient targets in tumors for both CD4 and CD8 T-cell-mediated therapies. (bmj.com)
  • 1 , 2 Largely expressed on the surface of SARS-CoV-2, the spike (S) protein plays a crucial role in binding to the host angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD) and facilitating viral entry, 3 , 4 which is therefore considered as one of the most preferred targets against SARS-CoV-2. (biorxiv.org)
  • Over 7,000 receptor-based pharmacophore models (covering 1,627 drug targets information, 459 of which are human protein targets) are stored and accessed by PharmMapper. (lilab-ecust.cn)
  • Protein subunits assembly is guided by the establishment of non-covalent interactions in the quaternary structure of the protein. (wikipedia.org)
  • Because those patients retain some cone function, we reasoned that mutant alleles encode functional channel subunits that alter the human cone visual pathway in characteristic ways. (jneurosci.org)
  • Based on primary sequence comparisons, β subunits are predicted to be modular structures composed of five domains (A-E) that are related to the large family of membrane-associated guanylate kinase proteins. (jneurosci.org)
  • At the center of protein-protein interactions are the binding surfaces, or interfacial residues which form contacts between binding partners and stabilize protein complexes. (biomedcentral.com)
  • Molecular analysis suggested that Esc2p contributed to silencing in a manner similar to Sir1p and probably helped recruit or stabilize the other Sir proteins, while Htz1p present at HMR assembled a specialized chromatin structure necessary for silencing (Dhillon, 2000). (sdbonline.org)
  • Protein location can be predicted either from the sequence of a protein alone by identification of targeting peptide sequences and motifs, or by homology to proteins of known location. (biomedcentral.com)
  • A third approach, which is complementary, exploits the differences in amino acid composition of proteins associated to different cellular locations, and can be useful if motif and homology information are missing. (biomedcentral.com)
  • A calponin homology domain is predicted in yeasst Cdc24p. (embl.de)
  • A protein complex assembly can result in the formation of homo-oligomeric or hetero-oligomeric complexes. (wikipedia.org)
  • Homo-oligomers are macromolecular complexes constituted by only one type of protein subunit. (wikipedia.org)
  • The latter is useful for revealing potential biological relationships between different complexes, and a suitable method to directly compare protein-protein interfaces across randomly selected protein complexes and to quantitatively assess their pairwise similarities is highly desirable. (biomedcentral.com)
  • Triangle network motifs predict complexes by complementing high-error interactomes with structural information. (leibniz-fli.de)
  • HDX-MS has emerged as a powerful tool to interrogate the structure and dynamics of proteins and their complexes. (silverchair.com)
  • HDX-MS, on the other hand, provides an extremely sensitive method for interrogating the conformational dynamics of proteins and their complexes via monitoring the exchange of hydrogens to deuterium [ 17-19 ]. (silverchair.com)
  • The hOAT3 cDNA consisted of 2179 base pairs that encoded a 543-amino-acid residue protein with 12 putative transmembrane domains. (aspetjournals.org)
  • Protein-protein interactions play important functional roles in almost all biological activities, including, but not restricted to, signal transduction, gene regulation, catalytic enzymatic activities and structural roles [ 1 ]. (biomedcentral.com)
  • Yet, these proteins play important roles in many processes that require the protein to interact with a number of other proteins. (elifesciences.org)
  • Membrane proteins play critical roles in higher organisms and are responsible for diverse cellular functions such as signalling and molecular transport. (silverchair.com)
  • Silencing at mating locus HMR requires silencers, and one of the roles of the silencer is to recruit Sir proteins. (sdbonline.org)
  • In this short review, we outline recent progresses in dissecting the conformational mechanisms of membrane proteins using HDX-MS. We further describe how the use of computational strategies can aid the interpretation of experimental data and enable visualisation of otherwise intractable membrane protein states. (silverchair.com)
  • While high resolution structures of membrane nanomachines are undeniably pertinent, our ability to leverage structure against function, requires us to have access to their conformational changes and functional states. (silverchair.com)
  • We applied time-independent component analysis (tICA) and protein connectivity network model, on all-atom molecular dynamics trajectories, to identify key non-RBD residues, playing crucial role in the conformational transition facilitating spike-receptor binding and infection of human cell. (biorxiv.org)
  • Based on the structure, we performed integrative analysis of the cellular trafficking, protein thermostability, ATP hydrolysis, and the transport activity of representative mutations. (elifesciences.org)
  • Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. (elifesciences.org)
  • Proteins perform their functions in associated cellular locations. (biomedcentral.com)
  • The cell's functional machinery - proteins - need to be present at specific cellular compartments so that cells can function properly. (biomedcentral.com)
  • therefore, cellular and molecular analyses of RTX and CA125 interaction were peformed, and a library of RTX variants was generated using a proprietary technology called Block‑Removed Immunoglobulin Technology that combines randomized amino acid substitutions and high‑throughput functional screenings to identify CA125‑refractory RTX variants. (spandidos-publications.com)
  • analyzed the amino acid sequences of two specific intrinsically disordered proteins from different organisms to reconstruct the versions of the proteins that were likely found in their common ancestors 450-600 million years ago. (elifesciences.org)
  • Calibration of the method using predicted values of amino acid exposure allows classifying proteins without 3D-information with an accuracy of 62% and discerning proteins in different locations even if they shared high levels of identity. (biomedcentral.com)
  • A number of actin-binding proteins, including spectrin, alpha-actinin and fimbrin, contain a 250 amino acid stretch called the actin binding domain (ABD). (embl.de)
  • 1987. Statistical correlations for predicting the partition coefficient for nonpolar organic contaminants between aquifer organic carbon and water. (cdc.gov)
  • Here, using atomistic molecular dynamics simulation, we study the correlations between the RBD dynamics with physically distant residues in the spike protein, and provide a deeper understanding of their role in the infection, including the prediction of important mutations and of distant allosteric binding sites for therapeutics. (biorxiv.org)
  • Structural comparison of protein-protein interfaces provides valuable insights into the functional relationship between proteins, which may not solely arise from shared evolutionary origin. (biomedcentral.com)
  • The currently available implementation for this method initially defines interfacial residues using atomic details, and then uses positions of the Cα atoms for structural alignment and scoring, and includes a sequence-order dependent version [ 10 ] and a sequence-order independent version [ 11 ]. (biomedcentral.com)
  • His calculations on protein circular dichroism spectroscopy, a key technique in structural biology, are the most accurate to be published. (nottingham.ac.uk)
  • Other emerging structural techniques such as pulsed electron double resonance (PELDOR or DEER) have contributed invaluable insights into membrane protein structural dynamics [ 4-6 ]. (silverchair.com)
  • Structural MS has emerged as a powerful tool for characterising protein structure and function, complementing high-resolution methods [ 7-9 ]. (silverchair.com)
  • 1991), none of the the structural details of the heterogeneous protein surface and experimental studies mentioned so far could provide un- takes into account a variety of short-range interactions, direct ambiguous information about oligomer structure. (lu.se)
  • Over the last decade, progresses in native MS have allowed the retention of intact membrane protein structures into the gas phase of a mass spectrometer and more spectacularly, to characterise lipid binding events to such proteins [ 9-16 ]. (silverchair.com)
  • Many are physical contacts with molecular associations between chains that occur in a cell or in a living organism in a specific biomolecular context. (wikipedia.org)
  • The p.Asn173His mutation affects a residue in the forkhead domain that is 100% conserved among vertebrate orthologs and is predicted to participate in protein-protein interactions. (molvis.org)
  • Mutation on these residues can lead to new strains of coronavirus with different degrees of infectivity and virulence. (biorxiv.org)
  • The most ubiquitous D614G mutation is predicted ab-initio from our model. (biorxiv.org)
  • Protein-protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and the hydrophobic effect. (wikipedia.org)
  • His research spans a wide range, from the quantum chemistry of small molecules and the spectroscopic properties of proteins, to the application of state-of-the-art statistical and computer science methodology to problems in bioinformatics, drug design and sustainable chemistry. (nottingham.ac.uk)
  • Large scale screening of therapeutic molecules and antibodies are underway aiming to target the spike protein and consequently prevent infection. (biorxiv.org)
  • ChemMapper is an online platform to predict polypharmacology effect and mode of action for small molecules based on 3D similarity computation. (lilab-ecust.cn)
  • The ancestral proteins were then 'resurrected' by recreating them in test tubes and their characteristics and properties analyzed with experimental and computational biophysical methods. (elifesciences.org)
  • 1997) at higher how proteins interact with themselves in solution. (lu.se)
  • One approach tries to identify motifs recognized by the sorting proteins and receptors of the protein transport machinery to move protein products from the cytosol to other subcellular locations [ 6 ]. (biomedcentral.com)
  • Infection of human cells by the novel coronavirus (SARS-Cov-2) involves the attachment of the receptor binding domain (RBD) of the spike protein to the peripheral membrane ACE2 receptors. (biorxiv.org)
  • developed I2I-SiteEngine [ 12 ] to compare the physicochemical properties of the functional groups forming protein-protein interfaces, which uses an algorithm similar to pharmacophore mapping. (biomedcentral.com)
  • The structure and functional studies of disease-causing mutations are solid and will appeal to the transporter and medical genetics communities. (elifesciences.org)
  • Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low-affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations. (elifesciences.org)
  • Significant research effort for drug design against COVID-19 is focused on the receptor binding domain of the spike protein, although this region is prone to mutations causing resistance against therapeutics. (biorxiv.org)
  • These residues can not only be targeted by broad spectrum antibodies and drugs, mutations in them can generate new strains of coronavirus resulting in future epidemic. (biorxiv.org)
  • 6 Significantly, the sites in S protein have been demonstrated to be vulnerable to acquire mutations. (biorxiv.org)
  • Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. (leibniz-fli.de)
  • PPI spider: a tool for the interpretation of proteomics data in the context of protein-protein interaction networks. (leibniz-fli.de)
  • NASCENT: An automatic protein interaction network generation tool for non-model organisms. (leibniz-fli.de)
  • Constructing glucagon like peptide-1 receptor fused with derivatives of GFP for visualizing protein-protein interaction in living cells. (leibniz-fli.de)
  • Small molecule protein-protein interaction inhibitors as CNS therapeutic agents: current progress and future hurdles. (leibniz-fli.de)
  • Fault tolerance in protein interaction networks: stable bipartite subgraphs and redundant pathways. (leibniz-fli.de)
  • We present an integrated platform called Pesticide-Target interaction database (PTID), which comprises a total of 1347 pesticides with rich annotation of ecotoxicological and toxicological data as well as 13 738 interactions of pesticide-target and 4245 protein terms via text mining. (lilab-ecust.cn)
  • Taking two user defined binding sites as reference and fitting structure, SiteMapper try to align these two structures in order to obtain a correspondence between residues from reference site and fitting site and evaluate the similarity between these two binding sites. (lilab-ecust.cn)
  • Adrenoleukodystrophy protein (ALDP) is responsible for the transport of very-long-chain fatty acids (VLCFAs) and corresponding CoA-esters across the peroxisomal membrane. (elifesciences.org)
  • The adrenoleukodystrophy protein (ALDP) or ABCD1 is an ABC transporter that participates in the transport of free very long-chain fatty acids and their CoA esters across the peroxisomal membrane. (elifesciences.org)
  • Deciphering soluble and membrane protein function using yeast systems. (leibniz-fli.de)
  • Recent advances in the methodology and instrumentation have enabled the application of HDX-MS to membrane proteins. (silverchair.com)
  • Developing new tools are therefore pertinent for improving our fundamental knowledge of how membrane proteins function in the cell. (silverchair.com)
  • Understanding the mechanism underpinning membrane-related function requires detailed characterisation of membrane protein structure and dynamics. (silverchair.com)
  • The hOAT3 protein was shown to be localized in the basolateral membrane of renal proximal tubules and the hOAT3 gene was determined to be located on the human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis. (aspetjournals.org)
  • Key regulators identified in this context include the STAT1:STAT2 heterodimer and interferon regulatory factor family proteins. (bvsalud.org)
  • absence of detection of known motifs cannot be used to imply that a protein remains in the cytosol. (biomedcentral.com)
  • For stage one, we trained multiple Support Vector Machines (SVMs) to score eukaryotic protein sequences for membership to each of three categories: nuclear, cytoplasmic and extracellular, plus extra category nucleocytoplasmic, accounting for the fact that a large number of proteins shuttles between those two locations. (biomedcentral.com)
  • Currently, most protein sequences in databases are the result of translation of hypothetical transcripts derived from genomic sequencing data [ 3 ]. (biomedcentral.com)
  • Given its ubiquitous nature, wide metabolic and functional impact of its inhibition, and lack of sequence conservation between prokaryotes and humans, the CoA pathway is therefore an attractive pathway for drug discovery for many different infectious diseases, including TB. (nature.com)
  • TFBSs are typically located upstream of target genes, within a few thousand base pairs of the transcription start site. (bvsalud.org)
  • However, a group of proteins called 'intrinsically disordered proteins' are flexible in their shape and lack a stable three-dimensional structure. (elifesciences.org)
  • 5 , 7 - 9 More specifically, a study analyzing 10,022 SARS-CoV-2 genomes from 68 countries revealed 2969 different missense variants, with 427 variants in the S protein. (biorxiv.org)
  • We developed a coarse-grained method, PCalign, to quantitatively evaluate physicochemical similarities between a given pair of protein-protein interfaces. (biomedcentral.com)
  • This method uses an order-independent algorithm, geometric hashing, to superimpose the backbone atoms of a given pair of interfaces, and provides a normalized scoring function, PC-score, to account for the extent of overlap in terms of both geometric and chemical characteristics. (biomedcentral.com)
  • PCalign is a useful method in recognizing shared chemical and spatial patterns among protein-protein interfaces. (biomedcentral.com)
  • While these approaches provide insights into the mechanism of protein-protein recognition, they are not suitable for measuring similarities between a given pair of protein-protein interfaces. (biomedcentral.com)
  • Gao and Skolnick developed the dynamic programming-based algorithm Ialign [ 10 ] to detect protein-protein interfaces with shared geometric patterns. (biomedcentral.com)
  • Predicting protein-protein interfaces as clusters of optimal docking area points. (leibniz-fli.de)
  • We developed a new algorithm for subcellular location prediction that uses residue exposure signatures. (biomedcentral.com)
  • Depending on the specific biological question being asked, methods for protein-protein interface comparison with different focuses have been developed. (biomedcentral.com)
  • Another aspect of Hirst's research focuses on the study of protein-ligand interactions, using techniques including QSAR, machine learning, neural networks, docking, molecular dynamics (MD) simulations and quantum chemistry. (nottingham.ac.uk)
  • The basis of hapten- molecular mechanisms of the sensitization pro- protein binding work is the hypothesis that upon cess will result in novel opportunities for the skin absorption, only protein-reactive chemicals development of alternative methods for assessing (or those that can be metabolically or chemically skin sensitization hazard and relative potency of converted to protein-reactive species) are able to chemicals. (cdc.gov)
  • While powerful, native MS alone, offers little information on protein dynamics. (silverchair.com)
  • Our model, based on time-independent component analysis (tICA) and protein graph connectivity network, was able to identify multiple residues, exhibiting long-distance coupling with the RBD opening dynamics. (biorxiv.org)
  • formation has come, not from solution studies, but from Whereas theoretical studies of protein self-association are crystallography. (lu.se)
  • The histone H2A.F/Z (H2AZ) variant is a functionally distinct, highly conserved histone subgroup that likely represents a separate evolutionary lineage of histone H2A proteins. (sdbonline.org)
  • In this study we explored the relationship between residue exposure and protein subcellular location. (biomedcentral.com)
  • Whilst elicitation of the symptoms of allergic contact computational sensitization hazard prediction dermatitis (ACD) upon subsequent exposure to rulebase tools such as Deduction and Estimation the same or cross-reactive chemicals. (cdc.gov)
  • Contact allergens are present in the natural mate potency and are not used as risk assessment environment, but the potential exposure to aller- tools in safety support (8). (cdc.gov)
  • In particular, the computational prediction of subcellular location from protein sequence information has been attempted mainly using three approaches. (biomedcentral.com)
  • Many molecular processes within a cell are carried out by molecular machines that are built from numerous protein components organized by their PPIs. (wikipedia.org)
  • Here we used cryo-EM to understand the molecular basis of these unique functional properties. (nature.com)
  • The findings shed light on fundamental principles of how new protein-protein interactions emerge and evolve on a molecular level. (elifesciences.org)
  • A deeper knowledge of how this molecular evolution happened will broaden our understanding of present day protein-protein interactions and might aid the design of drugs that can mimick proteins. (elifesciences.org)
  • One of the key molecular events in skin sensitization is protein haptenation, i.e. the chemical modification of self-skin protein(s) thus forming macromolecular immunogens. (cdc.gov)
  • Therefore, the study of protein function can be facilitated by predictions of protein location. (biomedcentral.com)
  • Homocitrullination of proteins occurs in tumors and can be targeted by CD4 T-cell responses. (bmj.com)
  • In addition, the CH domain occurs also in a number of proteins not known to bind actin, a notable example being the vav protooncogene. (embl.de)
  • Another important distinction to identify protein-protein interactions is the way they have been determined, since there are techniques that measure direct physical interactions between protein pairs, named "binary" methods, while there are other techniques that measure physical interactions among groups of proteins, without pairwise determination of protein partners, named "co-complex" methods. (wikipedia.org)
  • In many metabolic reactions, a protein that acts as an electron carrier binds to an enzyme that acts as its reductase. (wikipedia.org)
  • In the case of the mitochondrial P450 systems, the specific residues involved in the binding of the electron transfer protein adrenodoxin to its reductase were identified as two basic Arg residues on the surface of the reductase and two acidic Asp residues on the adrenodoxin. (wikipedia.org)
  • The specific order of amino acids in a protein determines its shape and structure, which in turn controls what the protein can do. (elifesciences.org)
  • 18 The human immune system started generating antibodies specific to residues outside RBD even at the earlier stage of the pandemic. (biorxiv.org)
  • On in vitro expression, only A3 T369S forms functional channels that display altered ion permeation, gating, ligand sensitivity, and low apparent affinity for extracellular Ca 2+ . (jneurosci.org)
  • Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. (cdc.gov)
  • Contact Dermatitis 2005: 53: 189-200 absence of in vivo animal data. (cdc.gov)
  • In this review, we consider some of the theoretical aspects of protein haptenation, how mechanisms of protein haptenation can be investigated experimentally and how we can use such knowledge in the development of novel, alternative approaches for predicting skin sensitization potential in the future. (cdc.gov)
  • Continued development of an empirical function for predicting and rationalizing protein-protein binding affinities. (leibniz-fli.de)
  • First, we found more functional contacts between the potential epileptogenic region and the whole brain, and more mainly unilateral FC maps in individuals compared to settings. (immune-source.com)
  • Background Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. (bmj.com)
  • A next step for the future will be to investigate how other protein-protein interactions have evolved and to identify general underlying patterns. (elifesciences.org)
  • Mutants of Sir1p were generated that are recruited to the silencer but are unable to silence, and these mutants were used to identify four proteins, Sir3p, Sir4p, Esc2p, and Htz1p, that when overexpressed, restored silencing. (sdbonline.org)
  • We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. (nature.com)
  • A targeting signal prediction is, in principle, more reliable than a predicted location based on a close protein ortholog (or on a protein domain), which is itself better than location predicted on the basis of protein composition alone. (biomedcentral.com)
  • Proteins containing only a single amino terminal CH domain. (embl.de)
  • Taxonomic distribution of proteins containing CH domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with CH domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing CH domain in the selected taxonomic class. (embl.de)
  • Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C-C Bond Formation CHEMISTRY-A EUROPEAN JOURNAL. (nottingham.ac.uk)
  • One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of cyanate with the lysine residues in the polypeptide chain. (bmj.com)
  • Decamer formation is opposed by electrostatic repulsion among numerous cationic residues confined within a narrow channel. (lu.se)
  • Classification of nonenzymatic homologues of protein kinases. (leibniz-fli.de)
  • These findings lead to a deeper understanding of the network of interdependencies between RNA-binding proteins and constitute a valuable element in the discussion on developmental homeostasis and pathological states in which the studied protein factors play a significant role. (bvsalud.org)
  • While this is true in general terms, there are many known exceptions for this rule (e.g. the proteins of the Lsg1 family of GTPases [ 9 ] or locations taken as known might be predicted or incorrect. (biomedcentral.com)
  • We evaluated the functional role of DEAD-box (DDX) RNA helicases, DDX5 and DDX17 in MBNL-dependent AS regulation. (bvsalud.org)
  • We propose that the BPTI decamer, with a heparin chain threading the decamer channel, plays a functional role in the mast cell. (lu.se)
  • Heterologous expression revealed that only one mutant forms functional channels, albeit with grossly altered properties, including changes in Ca 2+ blockage and permeation. (jneurosci.org)