扩散影响的理论和模拟，随机门控配体与埋藏部位结合。
Theory and simulation of diffusion-influenced, stochastically gated ligand binding to buried sites.
机构信息
Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA.
出版信息
J Chem Phys. 2011 Oct 14;135(14):145101. doi: 10.1063/1.3645000.
Abstract
We consider the diffusion-influenced rate coefficient of ligand binding to a site located in a deep pocket on a protein; the binding pocket is flexible and can reorganize in response to ligand entrance. We extend to this flexible protein-ligand system a formalism developed previously [A. M. Berezhkovskii, A, Szabo, and H.-X. Zhou, J. Chem. Phys. 135, 075103 (2011)] for breaking the ligand-binding problem into an exterior problem and an interior problem. Conformational fluctuations of a bottleneck or a lid and the binding site are modeled as stochastic gating. We present analytical and Brownian dynamics simulation results for the case of a cylindrical pocket containing a binding site at the bottom. Induced switch, whereby the conformation of the protein adapts to the incoming ligand, leads to considerable rate enhancement.
摘要
我们考虑位于蛋白质深口袋内的配体与位点结合的扩散影响的速率系数；结合口袋是灵活的，并可以响应配体进入而重新组织。我们将以前开发的[ A. M. Berezhkovskii，A. Szabo 和 H.-X. Zhou，J. Chem. Phys. 135, 075103 (2011)]的形式主义扩展到这个灵活的蛋白质 - 配体系统中，用于将配体结合问题分解为外部问题和内部问题。瓶颈或盖子和结合位点的构象波动被建模为随机门控。我们为包含底部结合位点的圆柱形口袋的情况提供了分析和布朗动力学模拟结果。诱导开关，即蛋白质的构象适应进入的配体，导致相当大的速率增强。
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