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BMC Chem Biol. 2012; 12: 2.
Published online Apr 5, 2012. doi:  10.1186/1472-6769-12-2
PMCID: PMC3471015
Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications
Hiroki Kobayashi,#1 Hiroko Harada,#1 Masaomi Nakamura,1 Yushi Futamura,1 Akihiro Ito,2 Minoru Yoshida,2 Shun-ichiro Iemura,3 Kazuo Shin-ya,3 Takayuki Doi,4 Takashi Takahashi,5 Tohru Natsume,3 Masaya Imoto,1 and Yasubumi Sakakibaracorresponding author1
1Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan
2Chemical Genetics Laboratory, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan
3National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan
4Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba, Sendai, 980-8578, Japan
5Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan
corresponding authorCorresponding author.
#Contributed equally.
Hiroki Kobayashi: kobayashihiroki/at/riken.jp; Hiroko Harada: e39976/at/jp.ibm.com; Masaomi Nakamura: nakamura/at/dna.bio.keio.ac.jp; Yushi Futamura: futamuray/at/riken.jp; Akihiro Ito: akihiro-i/at/riken.jp; Minoru Yoshida: yoshidam/at/riken.jp; Shun-ichiro Iemura: iemura-shun/at/aist.go.jp; Kazuo Shin-ya: k-shinya/at/aist.go.jp; Takayuki Doi: doi_taka/at/mail.pharm.tohoku.ac.jp; Takashi Takahashi: ttak/at/apc.titech.ac.jp; Tohru Natsume: t-natsume/at/aist.go.jp; Masaya Imoto: imoto/at/bio.keio.ac.jp; Yasubumi Sakakibara: yasu/at/bio.keio.ac.jp
Received November 15, 2011; Accepted April 5, 2012.
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.
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