Empirical estimation of the energetic contribution of individual interface residues in structures of protein-protein complexes

Guharoy, Mainak ; Chakrabarti, Pinak (2009) Empirical estimation of the energetic contribution of individual interface residues in structures of protein-protein complexes Journal of Computer-Aided Molecular Design, 23 (9). pp. 645-654. ISSN 0920-654X

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Official URL: http://www.springerlink.com/content/p15j9625201484...

Related URL: http://dx.doi.org/10.1007/s10822-009-9282-3

Abstract

We report a simple algorithm to scan interfaces in protein-protein complexes for identifying binding "hot spots". The change in side-chain solvent accessible area (ΔASA) of interface residues has been related to change in binding energy due to mutating interface residues to Ala (ΔΔG X → ALA) based on two criteria-hydrogen bonding across the interface and location in the interface core-both of which are major determinants in specific, high-affinity binding. These relationships are used to predict the energetic contribution of individual interface residues. The predictions are tested against 462 experimental X → ALA mutations from 28 interfaces with an average unsigned error of 1.04 kcal/mol. More than 80% of interface hot spots (with experimental ΔΔG ≥ 2 kcal/mol) could be identified as being energetically important. From the experimental values, Asp, Lys, Tyr and Trp are found to contribute most of the binding energy, burying >45 Å2 on average. The method described here would be useful to understand and interfere with protein interactions by assessing the energetic importance of individual interface residues.

Item Type:Article
Source:Copyright of this article belongs to Springer-Verlag.
Keywords:Protein-protein Interaction; Hot Spots in the Interface; Alanine Scanning Mutagenesis; Molecular Recognition; Binding Energy Prediction
ID Code:21478
Deposited On:22 Nov 2010 11:18
Last Modified:20 May 2011 09:55

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