A physical reference state unifies the structure-derived potential of mean force for protein folding and binding.

TitleA physical reference state unifies the structure-derived potential of mean force for protein folding and binding.
Publication TypeJournal Article
Year of Publication2004
AuthorsLiu, S, Zhang C, Zhou H, Zhou Y
JournalProteins
Volume56
Pagination93-101
Date Published2004 Jul 1
Abstract

Extracting knowledge-based statistical potential from known structures of proteins is proved to be a simple, effective method to obtain an approximate free-energy function. However, the different compositions of amino acid residues at the core, the surface, and the binding interface of proteins prohibited the establishment of a unified statistical potential for folding and binding despite the fact that the physical basis of the interaction (water-mediated interaction between amino acids) is the same. Recently, a physical state of ideal gas, rather than a statistically averaged state, has been used as the reference state for extracting the net interaction energy between amino acid residues of monomeric proteins. Here, we find that this monomer-based potential is more accurate than an existing all-atom knowledge-based potential trained with interfacial structures of dimers in distinguishing native complex structures from docking decoys (100% success rate vs. 52% in 21 dimer/trimer decoy sets). It is also more accurate than a recently developed semiphysical empirical free-energy functional enhanced by an orientation-dependent hydrogen-bonding potential in distinguishing native state from Rosetta docking decoys (94% success rate vs. 74% in 31 antibody-antigen and other complexes based on Z score). In addition, the monomer potential achieved a 93% success rate in distinguishing true dimeric interfaces from artificial crystal interfaces. More importantly, without additional parameters, the potential provides an accurate prediction of binding free energy of protein-peptide and protein-protein complexes (a correlation coefficient of 0.87 and a root-mean-square deviation of 1.76 kcal/mol with 69 experimental data points). This work marks a significant step toward a unified knowledge-based potential that quantitatively captures the common physical principle underlying folding and binding. A Web server for academic users, established for the prediction of binding free energy and the energy evaluation of the protein-protein complexes, may be found at http://theory.med.buffalo.edu.

Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/15162489?dopt=Abstract

Alternate JournalProteins
Citekey15162489