Nature is more a tinkerer rather than an inventor. Proteins share similar functional sites as paralogs or homologs, resulting in off-target (side) effects of so-called specific inhibitors. A small portion of compounds with tolerable side effects are approved by FDA, while the majority fail the clinical trials for their intolerable side effects. In this talk, I advocate with evidence that 2 or 3 FDA-approved drugs targeting the same disease protein could confer a specificity with minimized side effects. I will demonstrate our techniques to repurpose FDA-approved drugs for active site, protein-protein interaction interface, allosteric sites of an oncogenic enzyme, validated by a series of biochemical, structural biology, cell and animal experiments. One automated simulation-docking-simulation pipeline we have constructed 【DRDOCK】 provided a portion of our techniques to screen FDA drugs for a defined protein cavity for general researchers and pharmaceutical companies.
Dr. Lee-Wei Yang is a computational biologist with expertise in molecular structure analysis, dynamics, interaction and design. He is currently a Full Professor and the Director in the Institute of Bioinformatics and Structural Biology at National Tsing Hua University (NTHU), Taiwan. He also currently serves as the Founding Director of the PhD Program of Biomedical Artificial Intelligence, NTHU. Dr Yang had professional training in protein dynamics/molecular mechanics conducted at the School of Medicine, University of Pittsburgh (where he earned the PhD degree), University of Tokyo and Harvard University, he joined the College of Life Science in National Tsing Hua University, Taiwan, in Feb 2011. He currently has an H-index of 22 with >3150 citations from 40 SCI publications. He is also an honorary Professor in Mathematical Sciences, University of Liverpool, UK (Dual PhD Degree Program), a visiting Professor in I.P.R., University of Osaka (2018), a core member in TIGP PhD programs (Bioinformatics and CBMB), Academia Sinica, as well as a program coordinator in National Center for Theoretical Sciences (Physics division). He also served as the Division Director of International Students, Office of Global Affairs, National Tsing Hua University, from Aug, 2016 to Jan, 2019.