title: Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications.
abstract: BACKGROUND
  Identification of the target proteins of bioactive compounds is critical for elucidating the mode of action; however, target identification has been difficult in general, mostly due to the low sensitivity of detection using affinity chromatography followed by CBB staining and MS/MS analysis.
  
  
  RESULTS
  We applied our protocol of predicting target proteins combining in silico screening and experimental verification for incednine, which inhibits the anti-apoptotic function of Bcl-xL by an unknown mechanism. One hundred eighty-two target protein candidates were computationally predicted to bind to incednine by the statistical prediction method, and the predictions were verified by in vitro binding of incednine to seven proteins, whose expression can be confirmed in our cell system.As a result, 40% accuracy of the computational predictions was achieved successfully, and we newly found 3 incednine-binding proteins.
  
  
  CONCLUSIONS
  This study revealed that our proposed protocol of predicting target protein combining in silico screening and experimental verification is useful, and provides new insight into a strategy for identifying target proteins of small molecules.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Futamura
authors.affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
authors.forename: Shun-Ichiro
authors.initials: SI
authors.lastname: Iemura
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-Ya
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba, Sendai, 980-8578, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
authors.forename: Yasubumi
authors.initials: Y
authors.lastname: Sakakibara