Co-occurring atomic contacts for the characterization of protein binding hot spots

Publication Type:
Journal Article
PLoS ONE, 2015, 10 (12)
Issue Date:
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© 2015 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. A binding hot spot is a small area at a protein-protein interface that can make significant contribution to binding free energy. This work investigates the substantial contribution made by some special co-occurring atomic contacts at a binding hot spot. A co-occurring atomic contact is a pair of atomic contacts that are close to each other with no more than three covalent-bond steps.We found that two kinds of co-occurring atomic contacts can play an important part in the accurate prediction of binding hot spot residues. One is the co-occurrence of two nearby hydrogen bonds. For example, mutations of any residue in a hydrogen bond network consisting of multiple co-occurring hydrogen bonds could disrupt the interaction considerably. The other kind of co-occurring atomic contact is the co-occurrence of a hydrophobic carbon contact and a contact between a hydrophobic carbon atom and a π ring. In fact, this co-occurrence signifies the collective effect of hydrophobic contacts. We also found that the B-factor measurements of several specific groups of amino acids are useful for the prediction of hot spots. Taking the B-factor, individual atomic contacts and the co-occurring contacts as features, we developed a new prediction method and thoroughly assessed its performance via cross-validation and independent dataset test. The results show that our method achieves higher prediction performance than well-known methods such as Robetta, FoldX and Hotpoint.We conclude that these contact descriptors, in particular the novel co-occurring atomic contacts, can be used to facilitate accurate and interpretable characterization of protein binding hot spots.
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