| Info. | Vol.13 - No.3 (2019.09.20) |
|---|---|
| Title | Molecular Docking-assisted Protein Chip Screening of Inhibitors for Bcl-2 Family Protein-protein Interaction to Discover Anticancer Agents by Fragment-based Approach |
| Authors | Myoung-Schook Yoou1, Sungjoon Cho2 & Youngjin Choi2,3,* |
| Institutions | 1Department of Biomedical Laboratory, Korea Nazarene University, Cheonan, 31172, Republic of Korea 2School of Food and Pharmaceutical Engineering, Hoseo University, Asan 31499, Republic of Korea 3Research Institute for Basic Science & BioChip Research Center, Hoseo University, Asan 31499, Republic of Korea *Correspondence and requests for materials should be addressed to Y. Choi (ojchoi@hoseo.edu) |
| Abstract | For fragment-based cancer drug discovery, we introduced a molecular docking simulation combined with a protein chip assay. Protein chip technology was used to find fragment-hits that had inhibitory activity against Bcl-2 protein from 131 pre-selected fragment chemicals. Molecular docking simulation was performed for the 12 identified fragment-hits to establish the binding mode of these compounds in the Bcl-2 site. Using the molecular docking-assisted protein chip screening system, we derived a virtual compound structure with an important scaffold feature for interaction with the Bcl-2 protein. We then tested the anticancer activity of 26 compounds that were similar to the scaffold structure. The anticancer activity was confirmed by MTT-assay in A549 lung cancer cells. Finally, three chemicals showed dose-dependent inhibitory activity against cancer cell proliferation. We suggest that the present molecular docking-assisted protein chip assay can be used as a platform technology in the fragment-based drug development process to discover inhibitory agents of protein-protein interactions. |
| Keyword | Anticancer agents, Docking simulation, Drug screening, Molecular modelling, Protein chip |
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