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In Silico Chaperonin-Like Cycle Helps Folding of Proteins for Structure Prediction

Tadaomi Furuta ^*  ¶, Yoshimi Fujitsuka ^*, George Chikenji ^*  and Shoji Takada ^*  ¶

^* Department of Chemistry, Faculty of Science, and Graduate School of Science and Technology, Kobe University, Nada, Kobe, Japan; Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo, Japan; Department of Computational Science and Engineering, Graduate School of Engineering, Nagoya University, Chigusa, Nagoya, Japan; Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo, Kyoto, Japan; and ^¶ Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan

Correspondence: Address reprint requests to Shoji Takada, Tel.: 81-75-753-4220; E-mail: takada{at}biophys.kyoto-u.ac.jp.

Currently, one of the most serious problems in protein-folding simulations for de novo structure prediction is conformational sampling of medium-to-large proteins. In vivo, folding of these proteins is mediated by molecular chaperones. Inspired by the functions of chaperonins, we designed a simple chaperonin-like simulation protocol within the framework of the standard fragment assembly method: in our protocol, the strength of the hydrophobic interaction is periodically modulated to help the protein escape from misfolded structures. We tested this protocol for 38 proteins and found that, using a certain defined criterion of success, our method could successfully predict the native structures of 14 targets, whereas only those of 10 targets were successfully predicted using the standard protocol. In particular, for non--helical proteins, our method yielded significantly better predictions than the standard approach. This chaperonin-inspired protocol that enhanced de novo structure prediction using folding simulations may, in turn, provide new insights into the working principles underlying the chaperonin system.