报告题目: Free energy simulations with continuum solvation models: How well do they stand up in biomolecular simulations?
报 告 人: Associate Professor Ray Luo
Department of Molecular Biology and Biochemistry, University of California, Irvine, USA
报告地点: 生物药学楼 3-105
Continuum solvent models have become increasingly popular in biomolecular simulations. However their wide applications have revealed many limitations, such as improper balance of secondary structures, over population of salt-bridge interactions, and stabilityof proteins in molecular dynamics. These well-known limitations of continuum solvent models show that more developments are needed to fully establish the applications of these models in biomolecular simulations. In this talk, I will summarize our efforts to address how well these models can approximate explicit solvents. We have studied whether these models would break down when scaling from small organic molecules to typical-sized biomacromolecules. We have analyzed these models in the context of molecular dynamics simulations on simple systems such as dipeptides and peptides. We have also applied the continuum solvent-based free energy method to the more challenging protein-ligand binding calculations. Overall we have found good agreement with explicit solvents and with experiment when consistent calibration and testing is performed. We have also noticed limitations in these models that require further development. Finally, I will summarize our development of next-generation continuum solvation framework in the context of the community-wide developments of polarizable force fields. Our preliminary studies show that it is possible to achieve very good agreement with quantum mechanical calculations for tested molecules when the new contiuum solvation framework is used.
Dr Luo completed his doctorate in physical chemistry with a focus on computational analysis of biomolecular systems at University of Maryland at College Park in 1998. After a postdoctoral training at the University of California, San Francisco, he joined the Department of Molecular Biology and Biochemistry at the University of California, Irvine in 2001. Dr. Luo is a principle developer of AMBER, one of the widely used molecular modeling programs in computational biochemistry. The major efforts of his team are in the development of new continuum solvation methods and in the maintenance of the PBSA program and related modules for continuum solvation modeling in AMBER. Dr. Luo's research has been supported by National Institute of General Medical Sciences throughout the his tenure years at University of California.