Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications

Hiroki Kobayashi, Hiroko Harada, Masaomi Nakamura, Yushi Futamura, Akihiro Ito, Minoru Yoshida, Shun Ichiro Iemura, Kazuo Shin-Ya, Takayuki Doi, Takashi Takahashi, Tohru Natsume, Masaya Imoto, Yasubumi Sakakibara

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number2
JournalBMC Chemical Biology
Volume12
DOIs
Publication statusPublished - 2012

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Screening
Proteins
Computer Simulation
Affinity chromatography
Network protocols
Betaine
Affinity Chromatography
Carrier Proteins
Staining and Labeling
Molecules
incednine

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine

Cite this

Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications. / Kobayashi, Hiroki; Harada, Hiroko; Nakamura, Masaomi; Futamura, Yushi; Ito, Akihiro; Yoshida, Minoru; Iemura, Shun Ichiro; Shin-Ya, Kazuo; Doi, Takayuki; Takahashi, Takashi; Natsume, Tohru; Imoto, Masaya; Sakakibara, Yasubumi.

In: BMC Chemical Biology, Vol. 12, 2, 2012.

Research output: Contribution to journalArticle

Kobayashi, H, Harada, H, Nakamura, M, Futamura, Y, Ito, A, Yoshida, M, Iemura, SI, Shin-Ya, K, Doi, T, Takahashi, T, Natsume, T, Imoto, M & Sakakibara, Y 2012, 'Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications', BMC Chemical Biology, vol. 12, 2. https://doi.org/10.1186/1472-6769-12-2
Kobayashi, Hiroki ; Harada, Hiroko ; Nakamura, Masaomi ; Futamura, Yushi ; Ito, Akihiro ; Yoshida, Minoru ; Iemura, Shun Ichiro ; Shin-Ya, Kazuo ; Doi, Takayuki ; Takahashi, Takashi ; Natsume, Tohru ; Imoto, Masaya ; Sakakibara, Yasubumi. / Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications. In: BMC Chemical Biology. 2012 ; Vol. 12.
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