Seminar: (351) Developing computational methods to facilitate understanding of protein sequence-structure-function relationship
Speaker: Prof. Suwen Zhao, School of Life Science and Technology, ShanghaiTech University, China
Time: 2019-04-17 13:30 to 2019-04-17 14:30
Venue: Meeting room (406), Building 24
My research focuses on developing and applying methods to gain understanding of protein sequence-structure-function relationship. We work on enzymes and membrane proteins such as GPCRs. For enzymes, we have developed methods such as pathway docking, genome neighborhood network and solute binding protein guided pathway discovery. For GPCRs, several big problems in the GPCR field have not been well addressed, such as activation mechanism, biased signaling mechanism and partial agonism. Recently, we have developed a method that can quantitatively evaluate the residue-residue contact strength (RRCS) for a given protein structure. From analyzing the differences of RRCS in inactive and active states of GPCRs, for the first time, we discovered an allosteric pathway that directly links the ligand binding pocket and G protein binding pocket. This pathway is universal in class A GPCRs. Guided by the universal pathway, we can easily design constitutively active/inactive receptors that can facilitate structure and functional studies of GPCRs. RRCS method can be used to study the mechanisms of other allosteric system in the future.