Jing Zhang - Yale

Starts: 4:00 pm on Thursday, September 27, 2012
Ends: 5:00 pm on Thursday, September 27, 2012
Location: MCS 148

Title: Detecting and understanding combinatorial mutation patterns responsible for HIV drug resistance. Abstract: We propose a systematic approach for a better understanding of how HIV viruses employ various combinations of mutations to resist drug treatments, which is critical to developing new drugs and optimizing the use of existing drugs. By probabilistically modeling mutations in the HIV-1 protease or reverse transcriptase (RT) isolated from drug-treated patients, we present a statistical procedure that first detects mutation combinations associated with drug resistance and then infers detailed interaction structures of these mutations. The molecular basis of our statistical predictions is further studied by using molecular dynamics simulations and free energy calculations. We have demonstrated the usefulness of this systematic procedure on three HIV drugs, (Indinavir, Zidovudine, and Nevirapine), discovered unique interaction features between viral mutations induced by these drugs, and revealed the structural basis of such interactions. More advanced Bayesian models are also developed for transmitted drug resistance and cross-resistance for multiple drugs. This is a joint work with Tingjun Hou, Wei Wang, and Jun S. Liu. Ref: 1. Zhang, J., Hou, T., Wei, W., Liu, S.J. (2010) Detecting and understanding combinatorial mutation patterns responsible for HIV drug resistance. PNAS 107, 1321. 2. Systematic Investigation on interactions for HIV Drug Resistance and Cross-Resistance among Protease Inhibitors. (2012) Jing Zhang Tingjun Hou, Yang Liu, Gang Chen, Xiao Yang, Jun S Liu and Wei Wang. Accepted by Journal of Proteome Science & Computational Biology.