Title

Identification of hot spot residues at protein-protein interface

Authors

Lei Li, Bing Zhao, Zhanhua Cui, Jacob Gan, Meena Kishore Sakharkar and Pandjassarame Kangueane*

Affiliation

School of mechanical and aerospace engineering, Nanyang Technological University, Singapore 639798

E-mail*

mpandjassarame@ntu.edu.sg; * Corresponding author

Article Type

Hypothesis

Date

received February 4, 2006; revised March 27, 2006; accepted March 29, 2006; published online April 4, 2006

It is known that binding free energy of protein-protein interaction is mainly contributed by hot spot (high energy) interface residues. Here, we investigate the characteristics of hot spots by examining inter-atomic sidechain-sidechain interactions using a dataset of 296 alanine-mutated interface residues. Results show that hot spots participate in strong and energetically favorable sidechain-sidechain interactions. Subsequently, we describe a novel, yet simple ‘hot spot’ prediction model with an accuracy that is similar to many available approaches. The model is also shown to efficiently distinguish specific protein-protein interactions from non-specific interactions.

Keywords

protein-protein interaction; interface analysis; hot spot residues; inter-atomic interaction

Abbreviations:

BPTI = bovine pancreatic trypsin inhibitor; NA = number of atoms in a residue involving sidechain-sidechain interactions at the interface; NA_l = number of atoms with legitimate (favorable) sidechain-sidechain contacts; NA_il = number of atoms with illegitimate (unfavorable) sidechain-sidechain contacts; NC_l = number of legitimate (favorable) sidechain-sidechain contacts; NC_il = number of illegitimate (unfavorable) sidechain-sidechain contacts; PDB = protein databank; vdW = van der Waals; NPV = native predictive value; PPV = positive predictive value; SN = sensitivity; SP = specificity

Citation

Li et al., Bioinformation 1(4): 121-126 (2006)

Edited by

N. Srinivasan

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.