Dataset Information

PAIRpred: partner-specific prediction of interacting residues from sequence and structure.

ABSTRACT: We present a novel partner-specific protein-protein interaction site prediction method called PAIRpred. Unlike most existing machine learning binding site prediction methods, PAIRpred uses information from both proteins in a protein complex to predict pairs of interacting residues from the two proteins. PAIRpred captures sequence and structure information about residue pairs through pairwise kernels that are used for training a support vector machine classifier. As a result, PAIRpred presents a more detailed model of protein binding, and offers state of the art accuracy in predicting binding sites at the protein level as well as inter-protein residue contacts at the complex level. We demonstrate PAIRpred's performance on Docking Benchmark 4.0 and recent CAPRI targets. We present a detailed performance analysis outlining the contribution of different sequence and structure features, together with a comparison to a variety of existing interface prediction techniques. We have also studied the impact of binding-associated conformational change on prediction accuracy and found PAIRpred to be more robust to such structural changes than existing schemes. As an illustration of the potential applications of PAIRpred, we provide a case study in which PAIRpred is used to analyze the nature and specificity of the interface in the interaction of human ISG15 protein with NS1 protein from influenza A virus. Python code for PAIRpred is available at http://combi.cs.colostate.edu/supplements/pairpred/.

SUBMITTER: Minhas Fu

PROVIDER: S-EPMC4329725 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

PAIRpred: partner-specific prediction of interacting residues from sequence and structure.

Minhas Fayyaz ul Amir Afsar Fu Geiss Brian J BJ Ben-Hur Asa A

Proteins 20131206 7

We present a novel partner-specific protein-protein interaction site prediction method called PAIRpred. Unlike most existing machine learning binding site prediction methods, PAIRpred uses information from both proteins in a protein complex to predict pairs of interacting residues from the two proteins. PAIRpred captures sequence and structure information about residue pairs through pairwise kernels that are used for training a support vector machine classifier. As a result, PAIRpred presents a ...[more]

PMID: 24243399

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Project description:MotivationAccurate predictions of protein-binding residues (PBRs) enhances understanding of molecular-level rules governing protein-protein interactions, helps protein-protein docking and facilitates annotation of protein functions. Recent studies show that current sequence-based predictors of PBRs severely cross-predict residues that interact with other types of protein partners (e.g. RNA and DNA) as PBRs. Moreover, these methods are relatively slow, prohibiting genome-scale use.ResultsWe propose a novel, accurate and fast sequence-based predictor of PBRs that minimizes the cross-predictions. Our SCRIBER (SeleCtive pRoteIn-Binding rEsidue pRedictor) method takes advantage of three innovations: comprehensive dataset that covers multiple types of binding residues, novel types of inputs that are relevant to the prediction of PBRs, and an architecture that is tailored to reduce the cross-predictions. The dataset includes complete protein chains and offers improved coverage of binding annotations that are transferred from multiple protein-protein complexes. We utilize innovative two-layer architecture where the first layer generates a prediction of protein-binding, RNA-binding, DNA-binding and small ligand-binding residues. The second layer re-predicts PBRs by reducing overlap between PBRs and the other types of binding residues produced in the first layer. Empirical tests on an independent test dataset reveal that SCRIBER significantly outperforms current predictors and that all three innovations contribute to its high predictive performance. SCRIBER reduces cross-predictions by between 41% and 69% and our conservative estimates show that it is at least 3 times faster. We provide putative PBRs produced by SCRIBER for the entire human proteome and use these results to hypothesize that about 14% of currently known human protein domains bind proteins.Availability and implementationSCRIBER webserver is available at http://biomine.cs.vcu.edu/servers/SCRIBER/.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:Worldwide structural genomics projects continue to release new protein structures at an unprecedented pace, so far nearly 6000, but only about 60% of these proteins have any sort of functional annotation.We explored a range of features that can be used for the prediction of functional residues given a known three-dimensional structure. These features include various centrality measures of nodes in graphs of interacting residues: closeness, betweenness and page-rank centrality. We also analyzed the distance of functional amino acids to the general center of mass (GCM) of the structure, relative solvent accessibility (RSA), and the use of relative entropy as a measure of sequence conservation. From the selected features, neural networks were trained to identify catalytic residues. We found that using distance to the GCM together with amino acid type provide a good discriminant function, when combined independently with sequence conservation. Using an independent test set of 29 annotated protein structures, the method returned 411 of the initial 9262 residues as the most likely to be involved in function. The output 411 residues contain 70 of the annotated 111 catalytic residues. This represents an approximately 14-fold enrichment of catalytic residues on the entire input set (corresponding to a sensitivity of 63% and a precision of 17%), a performance competitive with that of other state-of-the-art methods.We found that several of the graph based measures utilize the same underlying feature of protein structures, which can be simply and more effectively captured with the distance to GCM definition. This also has the added the advantage of simplicity and easy implementation. Meanwhile sequence conservation remains by far the most influential feature in identifying functional residues. We also found that due the rapid changes in size and composition of sequence databases, conservation calculations must be recalibrated for specific reference databases.

Dataset Information

PAIRpred: partner-specific prediction of interacting residues from sequence and structure.

Publications

PAIRpred: partner-specific prediction of interacting residues from sequence and structure.

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