Speaker: Shao-Gui Wu
Beijing Computational Science Research Center
Abstract: Genetic transcription lies at the heart of important biological processes. Despite great experimental progresses being made in recent years, detailed structural and physical mechanisms remain elusive. In this work, we chose a single-subunit RNA polymerase (RNAP) from bacteriophase T7 as a model system. Translocation of the RNAP along DNA has been studied by both experimental and computational work. Single molecule experiments detected a small free energy bias between pre- and post- translocation states of T7 RNAP. Our previous modeling study suggested that the translocation energy bias aids nucleotide selection at the pre-insertion state. In current work, we are testing hypotheses made from the previous study and investigate conformational changes at atomistic details. Free energy changes involved in translocation process are calculated from molecular dynamics simulations. In particular, O-helix in the finger domain and Tyr639 residue near the active site are supposed to play important roles during each elongation cycle. Correspondingly, we examine closely the energy cost of Tyr639 fluctuating IN and OUT of the active site, as well as that of opening and closing of O-helix. Physical insight of polymerase transcription can be gained further by combing our current free energy studies at atomistic simulations with former kinetic modeling that links to experimental research.
Date&Time: December 14, 2012 (Friday), 14:30–15:30
Location: 606 Conference Room
