| 报告题目 | Unfolding Simulations of Di-domain Proteins: Crystallin and Survivin Examples |
| 报告人 | Prof. Chenglong Li |
| 报告人单位 | Medicinal Chemistry, Biophysics and Chemical Physics The Ohio State University |
| 报告时间 | 2012-11-23 |
| 报告地点 | 合肥微尺度物质科学国家实验室9004会议室 |
| 主办单位 | 合肥微尺度物质科学国家实验室 |
| 报告介绍 | 报告摘要：
To understand in vitro protein folding/unfolding at various physical conditions is important for gaining insights on connections among protein structure, dynamics and biological function in the molecular biophysics field. This talk discusses molecular dynamics simulations on two di-domain proteins, crystallin and survivin, in order to explore the relationship between folding and domain-domain interaction.
Combining replica-exchange MD (REMD) with potential of mean force (PMF) calculations, we found that crystallin folding follows a four-state kinetics with two partially folded intermediates, the C-term domain acting as folding ”seed” for N-term domain. On the other hand, survivin folding and domain interactions are intertwined throughout the folding processes.
For protein-ligand molecular recognition, there are always two schools of thought: the so-called “induced-fit” model and “population-shift” model. For survivin, we revealed a 3-4 kcal/mol free energy barrier along the reaction coordinate of a dimer interface modulator ABT8, and the complex is stabilized by the gain of the binding energies of the ligand. This free energy barrier might prohibit the reproduction of the experimental binding mode from the regular NTP-MD ensemble docking that we had tried. The combination of REMD generalized ensemble sampling with ensemble docking and free energy pathway analysis may provide a novel research protocol for the simulation of protein-ligand recognition. |
