Grubmüller Helmut
Theoretical and Computational Biophysics Department, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Methods Mol Biol. 2005;305:493-515. doi: 10.1007/978-1-59259-912-7_23.
Many proteins are molecular nano-machines, which perform their biological function via well-coordinated structural transitions. Often, these motions occur on much slower time scales than those accessible to conventional molecular dynamics techniques, which are limited to submicrosecond time scales by current computer technology. This is also true for ligand binding and unbinding reactions. Force probe simulations (or steered molecular dynamics) provide a powerful means to overcome this limitation, and thus to get insight into the atomistic mechanisms that underlie biological functions such as ligand binding. This chapter provides a basic introduction into this method. It further sketches a simple nonequilibrium statistical mechanics treatment that shows how to relate the results of force probe simulations to atomic force microscopy (AFM) or optical tweezer experiments. As an example, enforced unbinding simulations of streptavidin/biotin complexes are detailed.
许多蛋白质是分子纳米机器，它们通过协调良好的结构转变来执行其生物学功能。通常，这些运动发生的时间尺度比传统分子动力学技术所能达到的要慢得多，而传统分子动力学技术由于当前计算机技术的限制，只能达到亚微秒时间尺度。配体结合和解离反应也是如此。力探针模拟（或引导分子动力学）提供了一种强大的手段来克服这一限制，从而深入了解诸如配体结合等生物学功能背后的原子机制。本章对该方法进行了基本介绍。它还概述了一种简单的非平衡统计力学处理方法，展示了如何将力探针模拟的结果与原子力显微镜（AFM）或光镊实验联系起来。作为一个例子，详细介绍了链霉亲和素/生物素复合物的强制解离模拟。
