Nucleic Acids Research Advance Access originally published online on November 6, 2008
Nucleic Acids Research 2008 36(22):7078-7087; doi:10.1093/nar/gkn868
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Nucleic Acids Research, 2008, Vol. 36, No. 22 7078-7087
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Common physical basis of macromolecule-binding sites in proteins
1Institute of Biomedical Sciences, Academia Sinica, Taipei 115 and 2Department of Chemistry, National Tsing Hua University, Hsinchu 300 Taiwan
*To whom correspondence should be addressed. Tel: +886 2 2652 3031; Fax: +886 2 2788 7641; Email: carmay{at}gate.sinica.edu.tw
Received July 10, 2008. Revised September 18, 2008. Accepted October 18, 2008.
Protein–DNA/RNA/protein interactions play critical roles in many biological functions. Previous studies have focused on the different features characterizing the different macromolecule-binding sites and approaches to detect these sites. However, no common unique signature of these sites had been reported. Thus, this work aims to provide a ‘common’ principle dictating the location of the different macromolecule-binding sites founded upon fundamental principles of binding thermodynamics. To achieve this aim, a comprehensive set of structurally nonhomologous DNA-, RNA-, obligate protein- and nonobligate protein-binding proteins, both free and bound to their respective macromolecules, was created and a novel strategy for detecting clusters of residues with electrostatic or steric strain given the protein structure was developed. The results show that regardless of the macromolecule type, the binding strength and conformational changes upon binding, macromolecule-binding sites are energetically less stable than nonmacromolecule-binding sites. They also reveal new energetic features distinguishing DNA- from RNA-binding sites and obligate protein- from nonobligate protein-binding sites in both free/bound protein structures.