Theoretical study of molecular mechanism of protein functions

我们开发了新的分子模拟方法来阐明蛋白质功能的分子机制。通过开发的方法，我们从理论上分析了酶促反应和蛋白质的整体构象变化。我们开发了一种QM/MM自由能法（QM/MM RWFE-SCF），使人们能够在分析酶反应路径时非常有效地考虑蛋白质结构波动。我们通过该方法揭示了相邻蛋白环的大构象变化在淀粉酶的酶催化中起着至关重要的作用。该方法还应用于微生物视紫红质颜色变异的结构建模。为了模拟蛋白质的大尺度构象变化，我们在线性响应理论的基础上提出了线性响应路径跟踪方法。我们应用该方法模拟了钙调蛋白在离子结合时的大尺度构象变化，并成功地用极短的MD计算预测了构象变化。

We have developed novel methodologies of molecular simulations to elucidate molecular mechanisms of protein functions. By the methodologies developed, we theoretically analyzed enzymatic reactions and global conformational changes of proteins. We developed a QM/MM free energy method (QM/MM RWFE-SCF) that enables one to very efficiently take into account protein structural fluctuation in analysis of enzymatic reaction paths. We revealed by the method that large conformational changes of an adjacent protein loop play a crucial role in enzymatic catalysis of □amylase. The method was also applied to structural modeling of color variants of microbial rhodopsins. For simulations of large scale conformational changes of proteins, we developed the linear response path following method based on a linear response theory. We applied the method to simulations of large scale conformational changes of calmodulin upon ion bindings, and successfully predicted the conformational changes with very short MD calculations.