The free energy landscape for β hairpin folding in explicit water

The folding free energy landscape of the C-terminal β hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and oplsaa force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the β strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The β hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.

本研究针对蛋白G（protein G）的C端β发夹（C-terminal β hairpin）的折叠自由能景观展开探究，模拟体系采用显式溶剂（explicit solvent）、周期性边界条件（periodic boundary condition）以及OPLSAA力场（OPLSAA force field）。本研究采用结合分子动力学轨迹与温度交换蒙特卡洛（Monte Carlo）过程的高度并行副本交换方法，并借助新型高效算法P3ME/RESPA完成构象采样。模拟结果显示，疏水核心（hydrophobic core）与β链氢键（β strand hydrogen bond）的形成时间大致同步。研究发现，针对各类反应坐标（reaction coordinate）的自由能景观在低温下呈现粗糙形貌，而在约360 K时转变为平滑的类漏斗状景观。与部分近期相关研究不同，本研究在所有测试温度下的模拟中均未观测到显著的螺旋含量（helical content）。在生理温度（biological temperature）下，β发夹构象占比与氢键形成概率的模拟结果与实验数据吻合度较好，但二者随温度升高的衰减速率均慢于实验观测结果。