Flexible dynamics of proteins and their functions

通过3年的项目，我们开发了新的蛋白质动力学计算方法，并研究了蛋白质功能的过程。(1)提出了一种新的粗粒度蛋白质动力学模拟方法，并将其应用于肌动球蛋白系统的力生成过程。发现了摆臂摆动和肌球蛋白头滑动运动的协同效应。(2)利用GO类模型研究了蛋白质的折叠过程。近对称蛋白质折叠过程的复杂性，揭示了多种途径的共存和其中的特定路径的选择机制。(3)通过分析光敏蛋白的功能过程，提出了功能漏斗的概念。(4)提出了一种新的模拟蛋白质折叠过程的方法，从序列中预测蛋白质的三维结构。我们参加了国际结构预测竞赛CASP7，并在新褶皱预测类别中获得了相当好的成绩。(5)用计算机模拟序列选择。我们发现，通过选择在活性位点具有所需局部构型的序列，随机序列可以进化成可折叠的蛋白质样序列。(6)通过分子动力学模拟研究了纳米尺度溶质周围的疏水水化现象，发现纳米尺度溶质周围存在拓扑敏感的水化现象和疏水相互作用。

Trough the 3-year project, we have developed new methods of computation of protein dynamics and investigated processes of protein functioning.(1) A coarse-grained method to simulate protein dynamics was newly developed and applied to the force-generation process of actomyosin system. Cooperative effects of the lever-arm swinging motion and the sliding motion of myosin head were found.(2) Folding process of proteins were investigated by using GO-like models. Complexity in the folding process of nearly symmetrical proteins was revealed by showing the co-existence of multiple pathways and the mechanism of selection of specific routes among them.(3) A novel concept of functional funnel was introduced by analyzing the functioning process of a photo-sensing protein.(4) 3-D structures of proteins were predicted from sequences by developing a new method to simulate the folding process. We attended the international contest for structure prediction, CASP7, and acquired fairly good scores in a category of new-fold prediction.(5) Sequence selection was simulated by computer. We found that by selecting sequences which have desired local configuration at the active-site, random sequences can evolve into the foldable protein-like sequences.(6) Hydrophobic hydration around the nano-meter size solutes were investigated by molecular dynamics simulation and the topology-sensitive hydration and hydrophobic interaction were found.