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Title: Crucial importance of the water-entropy effect in predicting hot spots in protein-protein complexes.
Authors: Oshima, Hiraku
Yasuda, Satoshi
Yoshidome, Takashi
Ikeguchi, Mitsunori
Kinoshita, Masahiro  kyouindb  KAKEN_id
Author's alias: 木下, 正弘
Issue Date: 15-Aug-2011
Publisher: Royal Society of Chemistry
Journal title: Physical chemistry chemical physics : PCCP
Volume: 13
Issue: 36
Start page: 16236
End page: 16246
Abstract: Hot spots" are residues accounting for the majority of the protein-protein binding free energy (BFE) despite that they comprise only a small fraction of the protein-protein interface. A hot spot can be found experimentally by measuring the BFE change upon mutating it to alanine: the mutation gives rise to a significantly large increase in the BFE. Theoretical prediction of hot spots is an enthusiastic subject in biophysics, biochemistry, and bioinformatics. For the development of a reliable prediction method, it is essential to understand the physical origin of hot spots. To this end, we calculate the water-entropy gains upon binding both for a wild-type complex and for its mutant complex using a hybrid method of the angle-dependent integral equation theory applied to a molecular model for water and the morphometric approach. We note that this type of calculation has never been employed in the previously reported methods. The BFE change due to alanine mutation is evaluated only from the change in the water-entropy gain with no parameters fitted to the experimental data. It is shown that the overall performance of predicting hot spots in our method is higher than that in Robetta, a standard free-energy-based method using fitting parameters, when the most widely used criterion for defining an actual hot spot is adopted. This result strongly suggests that the water-entropy effect we calculate is the key factor governing basic physics of hot spots.
Rights: © Royal Society of Chemistry 2011.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1039/c1cp21597c
PubMed ID: 21842056
Appears in Collections:Journal Articles

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