2018.06.23 Application of Parallel Continuous Simulated Tempering (PCST) to Cryo-EM structural refinement
题 目：Application of Parallel Continuous Simulated Tempering (PCST) to Cryo-EM structural refinement at near-atomic resolution
报告人：Dr. Jianpeng Ma
Professor of Bioengineering, Rice University
Lodwick T. Bolin Professor of Biochemistry, Baylor College of Medicine
Cryo-electron microscopy (Cryo-EM) has emerged as a promising technique for understanding molecular mechanisms of fundamental biological processes. Hardware advances in recent years have allowed near atomic to atomic-resolution single-particle Cryo-EM reconstruction for many macromolecular assemblies. However, model building and structural refinement at near atomic resolution remains a challenging task in the field. Our lab recently developed a powerful Parallel Continuous Simulated Tempering (PCST) algorithm that is highly efficient in accelerating barrier crossing and finding native structures than the conventional simulated annealing method. In this study, we used the PCST algorithm to refine Cryo-EM structures at near-atomic resolution in three systems at 6.8~8.0 Å resolution. Our results suggest that PCST-assisted Cryo-EM structural refinement not only significantly improved geometry statistics in terms of favored Ramachandran and rotamer distribution, but also enhanced the effective resolution of the resultant structural model by revealing many more native contacts that are only seen in atomic-resolution structures. In summary, PCST-assisted refinement represents an invaluable tool for Cryo-EM structural refinement.
Dr. Jianpeng Ma is a professor of Bioengineering at Rice University and the Lodwick T. Bolin Professor of Biochemistry at Baylor College of Medicine. He graduated from Fudan University with a Bachelor's degree of Chemistry in 1985. He received his Ph.D. in Chemistry at Boston University in 1996. Then he took up a postdoc in Computational Biophysics at Harvard University from 1996 to 2000.
Pro. Jianpeng Ma investigates the relationship between structure and function in biological molecules through computational biophysics, structural biology and the development of mathematical algorithms for computer simulation; supramolecular complexes; computer-aided drug designs; and structural refinement strategies.
Prof. Ma is a pioneer in the field of biophysics and leading expert in developing computational methods that have substantially expanded the ability to simulate, model and refine flexible biomolecular systems based on experimental data at low to intermediate resolutions.
To conduct his investigations in computational biophysics and structural biology, prof. Ma develops mathematical algorithms for the computer simulation of supramolecular complexes, computer-aided drug designs, and structural refinement strategies for experimental methods (x-ray crystallography and electron microscopy reconstruction). He is an expert in using x-ray crystallography to decipher the exact 3-D arrangement of atoms.