Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
J Phys Chem B. 2010 Sep 16;114(36):11866-74. doi: 10.1021/jp1031459.
An allosteric model is used to describe changes in lifetimes of biological receptor-ligand bonds subjected to an external force. Force-induced transitions between the two states of the allosteric site lead to changes in the receptor conformation. The ligand bound to the receptor fluctuates between two different potentials formed by the two receptor conformations. The effect of the force on the receptor-ligand interaction potential is described by the Bell mechanism. The probability of detecting the ligand in the bound state is found to depend on the relaxation times of both ligand and allosteric sites. An analytic expression for the bond lifetime is derived as a function of force. The formal theoretical results are used to explain the anomalous force and time dependences of the integrin-fibronectin bond lifetimes measured by atomic force microscopy (Kong, F.; et al J. Cell Biol. 2009, 185, 1275-1284). The analytic expression and model parameters describe very well all anomalous dependences identified in the experiments.
采用变构模型来描述生物受体-配体键在外力作用下的寿命变化。变构部位的两个状态之间的力诱导跃迁导致受体构象发生变化。与受体结合的配体在由两种受体构象形成的两个不同势之间波动。力对受体-配体相互作用势的影响由 Bell 机制来描述。发现在结合状态下检测到配体的概率取决于配体和变构部位的弛豫时间。作为力的函数，推导出键寿命的解析表达式。正式的理论结果用于解释原子力显微镜测量的整合素-纤连蛋白键寿命的异常力和时间依赖性（Kong，F.；等 J. Cell Biol. 2009, 185, 1275-1284）。解析表达式和模型参数很好地描述了实验中确定的所有异常依赖性。
