A protein domain interaction interface database: InterPare

Substitutions of individual amino acids in proteins may be under very different evolutionary restraints depending on their structural and functional roles. The Environment Specific Substitution Table (ESST) describes the pattern of substitutions in terms of amino acid location within elements of secondary structure, solvent accessibility, and the existence of hydrogen bonds between side chains and neighbouring amino acid residues. Clearly amino acids that have very different local environments in their functional state compared to those in the protein analysed will give rise to inconsistencies in the calculation of amino acid substitution tables. Here, we describe how the calculation of ESSTs can be improved by discarding the functional residues from the calculation of substitution tables. Four categories of functions are examined in this study: protein–protein interactions, protein–nucleic acid interactions, protein–ligand interactions, and catalytic activity of enzymes. Their contributions to residue conservation are measured and investigated. We test our new ESSTs using the program CRESCENDO, designed to predict functional residues by exploiting knowledge of amino acid substitutions, and compare the benchmark results with proteins whose functions have been defined experimentally. The new methodology increases the Z-score by 98% at the active site residues and finds 16% more active sites compared with the old ESST. We also find that discarding amino acids responsible for protein–protein interactions helps in the prediction of those residues although they are not as conserved as the residues of active sites. Our methodology can make the substitution tables better reflect and describe the substitution patterns of amino acids that are under structural restraints only.

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“…InterPare [18] was based on SCOP [19] version 1.71. The “Feature Identifier” is only for UniProt annotations.…”

Section: Resultsmentioning

confidence: 99%

Discarding Functional Residues from the Substitution Table Improves Predictions of Active Sites within Three-Dimensional Structures

Gong

Blundell

2008

PLoS Comput Biol

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“…Although not formally a database, the ProteinProtein Docking Benchmark [69], a collection of 84 nonredundant protein complexes for which both the bound and unbound structures are available, provides a valuable resource for testing new docking algorithms. Several further databases of structural protein-protein interaction data have been compiled, e.g., PQS [92,93], DIP [94], BIND [95], DIMER [96], BID [97], 3DID [98], PIBASE [99], iPfam [100], Interdom [101], Interpare [102], 3D Complex [103], Dockground [104], I2I [105], SCOPPI [106], and PROTCOM [107]. Most of these databases provide at least the identities of domain interface residues, along with interface statistics such as residue propensities and buried surface areas.…”

Section: Structural Protein-protein Interaction Databasesmentioning

confidence: 99%

Recent Progress and Future Directions in Protein-Protein Docking

Ritchie

2008

CPPS

296

203

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This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking algorithms employ a range of efficient search and scoring strategies, including e.g. fast Fourier transform correlations, geometric hashing, and Monte Carlo techniques. These approaches can often produce a relatively small list of up to a few thousand orientations, amongst which a near-native binding mode is often observed. However, despite the use of improved scoring functions which typically include models of desolvation, hydrophobicity, and electrostatics, current algorithms still have difficulty in identifying the correct solution from the list of false positives, or decoys. Nonetheless, significant progress is being made through better use of bioinformatics, biochemical, and biophysical information such as e.g. sequence conservation analysis, protein interaction databases, alanine scanning, and NMR residual dipolar coupling restraints to help identify key binding residues. Promising new approaches to incorporate models of protein flexibility during docking are being developed, including the use of molecular dynamics snapshots, rotameric and off-rotamer searches, internal coordinate mechanics, and principal component analysis based techniques. Some investigators now use explicit solvent models in their docking protocols. Many of these approaches can be computationally intensive, although new silicon chip technologies such as programmable graphics processor units are beginning to offer competitive alternatives to conventional high performance computer systems. As cryo-EM techniques improve apace, docking NMR and X-ray protein structures into low resolution EM density maps is helping to bridge the resolution gap between these complementary techniques. The use of symmetry and fragment assembly constraints are also helping to make possible docking-based predictions of large multimeric protein complexes. In the near future, the closer integration of docking algorithms with protein interface prediction software, structural databases, and sequence analysis techniques should help produce better predictions of protein interaction networks and more accurate structural models of the fundamental molecular interactions within the cell.

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“…One definition of contact residues/atoms uses atomic distance (Ofran and Rost 2003;Tsai et al 1996;Gong et al 2005;Lawrence and Colman 1993;Larsen et al 1998;Preissner et al 1998;Korkin et al 2005;Davis and Sali 2005). The measure under this definition evaluates how two residues/atoms are spatially close from interacting proteins.…”

Section: Definition Of Protein Interfaces: An Intractable But Fundamementioning

confidence: 99%

Protein Binding Interfaces and Their Binding Hot Spot Prediction: A Survey

Liu

2013

Translational Bioinformatics

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In living organisms, genes are the blueprints or library, specifying instructions for building proteins. Proteins constitute the bulk of cells. Proteins mutual binding and interactions play a vital role in numerous functions and activities, such as signal transduction, enzymatic reactions, immunoreactions and inter-cellular communications. This survey provides basic knowledge of proteins and protein binding. First, we describe proteins' fundamental elements, structures and functions. In Sect. 5.2, we present concepts related to protein binding and interactions. In Sect. 5.3, we explain why protein binding interfaces have a uneven distribution of binding free energy. In the Sects. 5.4 and 5.5, we explain why protein interfaces are complicated and how the current studies deal with this difficult problem. In Sect. 5.6, we present an overview on methods to model and predict binding free energy of protein interactions. Section 5.7 concludes this survey with a summary.

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A protein domain interaction interface database: InterPare

Cited by 46 publications

References 43 publications

Discarding Functional Residues from the Substitution Table Improves Predictions of Active Sites within Three-Dimensional Structures

Discarding Functional Residues from the Substitution Table Improves Predictions of Active Sites within Three-Dimensional Structures

Recent Progress and Future Directions in Protein-Protein Docking

Protein Binding Interfaces and Their Binding Hot Spot Prediction: A Survey

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