feature-based approach to modeling protein-protein interaction hot spots
Identifying features that effectively represent the energetic contribution of an individual interface residue to the interactions between proteins remains problematic. Here, we present several new features and show that they are more effective than conventional features. By combining the proposed fe...
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Published in | Nucleic acids research Vol. 37; no. 8; pp. 2672 - 2687 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.05.2009
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Identifying features that effectively represent the energetic contribution of an individual interface residue to the interactions between proteins remains problematic. Here, we present several new features and show that they are more effective than conventional features. By combining the proposed features with conventional features, we develop a predictive model for interaction hot spots. Initially, 54 multifaceted features, composed of different levels of information including structure, sequence and molecular interaction information, are quantified. Then, to identify the best subset of features for predicting hot spots, feature selection is performed using a decision tree. Based on the selected features, a predictive model for hot spots is created using support vector machine (SVM) and tested on an independent test set. Our model shows better overall predictive accuracy than previous methods such as the alanine scanning methods Robetta and FOLDEF, and the knowledge-based method KFC. Subsequent analysis yields several findings about hot spots. As expected, hot spots have a larger relative surface area burial and are more hydrophobic than other residues. Unexpectedly, however, residue conservation displays a rather complicated tendency depending on the types of protein complexes, indicating that this feature is not good for identifying hot spots. Of the selected features, the weighted atomic packing density, relative surface area burial and weighted hydrophobicity are the top 3, with the weighted atomic packing density proving to be the most effective feature for predicting hot spots. Notably, we find that hot spots are closely related to π-related interactions, especially π · · · π interactions. |
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Bibliography: | istex:6F64BE211917EB9310D4D1CCE880E9BF21BE9028 ArticleID:gkp132 ark:/67375/HXZ-SKSN828B-D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Feature-3 ObjectType-Undefined-2 |
ISSN: | 0305-1048 1362-4962 |
DOI: | 10.1093/nar/gkp132 |