title: Prediction of Ligand Binding Affinity by the Combination of Replica-Exchange Method and Double-Decoupling Method.
abstract: A prediction method for ligand binding affinities to proteins is proposed. We first predict the structures of protein-ligand complex by the replica-exchange umbrella sampling or its extension. We then calculate ligand binding affinities based on these predicted ligand-protein bound structures by the double-decoupling method. As a test of the effectiveness of the proposed method, we applied it to the system of the oncoprotein MDM2 and a ligand. The value of the predicted binding affinity turned out to be in good agreement with that from experiments.
authors.affiliation: Department of Physics, Graduate School of Science, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.|Structural Biology Research Center, Graduate School of Science, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.|Center for Computational Science, Graduate School of Engineering, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan.|Information Technology Center, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., 26-1 Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8585, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kokubo
authors.affiliation: Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., 26-1 Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8585, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tanaka