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Combining physicochemical and evolutionary information for protein contact prediction.

ABSTRACT: We introduce a novel contact prediction method that achieves high prediction accuracy by combining evolutionary and physicochemical information about native contacts. We obtain evolutionary information from multiple-sequence alignments and physicochemical information from predicted ab initio protein structures. These structures represent low-energy states in an energy landscape and thus capture the physicochemical information encoded in the energy function. Such low-energy structures are likely to contain native contacts, even if their overall fold is not native. To differentiate native from non-native contacts in those structures, we develop a graph-based representation of the structural context of contacts. We then use this representation to train an support vector machine classifier to identify most likely native contacts in otherwise non-native structures. The resulting contact predictions are highly accurate. As a result of combining two sources of information--evolutionary and physicochemical--we maintain prediction accuracy even when only few sequence homologs are present. We show that the predicted contacts help to improve ab initio structure prediction. A web service is available at http://compbio.robotics.tu-berlin.de/epc-map/.

SUBMITTER: Schneider M

PROVIDER: S-EPMC4206277 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Combining physicochemical and evolutionary information for protein contact prediction.

Schneider Michael M Brock Oliver O

PloS one 20141022 10

We introduce a novel contact prediction method that achieves high prediction accuracy by combining evolutionary and physicochemical information about native contacts. We obtain evolutionary information from multiple-sequence alignments and physicochemical information from predicted ab initio protein structures. These structures represent low-energy states in an energy landscape and thus capture the physicochemical information encoded in the energy function. Such low-energy structures are likely ...[more]

PMID: 25338092

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Project description:BackgroundPredicting protein contacts solely based on sequence information remains a challenging problem, despite the huge amount of sequence data at our disposal. Mutual Information (MI), an information theory measure, has been extensively employed and modified to identify residues within a protein (intra-protein) that are in contact. More recently MI and its variants have also been used in the prediction of contacts between proteins (inter-protein).MethodsHere we assess the predictive power of MI and variants for domain-domain contact prediction. We test original MI and these variants, which are called MIp, MIc and ZNMI, on 40 domain-domain test cases containing 10,753 sequences. We also propose and evaluate two new versions of MI that consider triangles of residues and the physiochemical properties of the amino acids, respectively.ResultsWe found that all versions of MI are skewed towards predicting surface residues. Since domain-domain contacts are on the surface of each domain, we considered only surface residues when attempting to predict contacts. Our analysis shows that MIc is the best current MI domain-domain contact predictor. At 20% recall MIc achieved a precision of 44.9% when only surface residues were considered. Our triangle and reduced alphabet variants of MI highlight the delicate trade-off between signal and noise in the use of MI for domain-domain contact prediction. We also examine a specific "successful" case study and demonstrate that here, when considering surface residues, even the most accurate domain-domain contact predictor, MIc, performs no better than random.ConclusionsAll tested variants of MI are skewed towards predicting surface residues. When considering surface residues only, we find MIc to be the best current MI domain-domain contact predictor. Its performance, however, is not as good as a non-MI based contact predictor, i-Patch. Additionally, the intra-protein contact prediction capabilities of MIc outperform its domain-domain contact prediction abilities.

Project description:BackgroundThe vitamins are important cofactors in various enzymatic-reactions. In past, many inhibitors have been designed against vitamin binding pockets in order to inhibit vitamin-protein interactions. Thus, it is important to identify vitamin interacting residues in a protein. It is possible to detect vitamin-binding pockets on a protein, if its tertiary structure is known. Unfortunately tertiary structures of limited proteins are available. Therefore, it is important to develop in-silico models for predicting vitamin interacting residues in protein from its primary structure.ResultsIn this study, first we compared protein-interacting residues of vitamins with other ligands using Two Sample Logo (TSL). It was observed that ATP, GTP, NAD, FAD and mannose preferred {G,R,K,S,H}, {G,K,T,S,D,N}, {T,G,Y}, {G,Y,W} and {Y,D,W,N,E} residues respectively, whereas vitamins preferred {Y,F,S,W,T,G,H} residues for the interaction with proteins. Furthermore, compositional information of preferred and non-preferred residues along with patterns-specificity was also observed within different vitamin-classes. Vitamins A, B and B6 preferred {F,I,W,Y,L,V}, {S,Y,G,T,H,W,N,E} and {S,T,G,H,Y,N} interacting residues respectively. It suggested that protein-binding patterns of vitamins are different from other ligands, and motivated us to develop separate predictor for vitamins and their sub-classes. The four different prediction modules, (i) vitamin interacting residues (VIRs), (ii) vitamin-A interacting residues (VAIRs), (iii) vitamin-B interacting residues (VBIRs) and (iv) pyridoxal-5-phosphate (vitamin B6) interacting residues (PLPIRs) have been developed. We applied various classifiers of SVM, BayesNet, NaiveBayes, ComplementNaiveBayes, NaiveBayesMultinomial, RandomForest and IBk etc., as machine learning techniques, using binary and Position-Specific Scoring Matrix (PSSM) features of protein sequences. Finally, we selected best performing SVM modules and obtained highest MCC of 0.53, 0.48, 0.61, 0.81 for VIRs, VAIRs, VBIRs, PLPIRs respectively, using PSSM-based evolutionary information. All the modules developed in this study have been trained and tested on non-redundant datasets and evaluated using five-fold cross-validation technique. The performances were also evaluated on the balanced and different independent datasets.ConclusionsThis study demonstrates that it is possible to predict VIRs, VAIRs, VBIRs and PLPIRs from evolutionary information of protein sequence. In order to provide service to the scientific community, we have developed web-server and standalone software VitaPred (http://crdd.osdd.net/raghava/vitapred/).

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Combining physicochemical and evolutionary information for protein contact prediction.

Publications

Combining physicochemical and evolutionary information for protein contact prediction.

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