Molecular dynamics study of unbinding of the avidin-biotin complex
Molecular dynamics study of unbinding of the avidin-biotin complex
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DOI：
10.1016/s0006-3495(97)78804-0
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发表时间：
1997-04-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Izrailev, S;Stepaniants, S;Schulten, K
我们报告的分子动力学模拟诱导，在40-500 ps的时间内，生物素从抗生物素蛋白的解结合通过外部谐波力与力常数接近的原子力显微镜杠杆。所施加的力足够大，以降低总结合能，足以在测量时间内产生解结合。我们的研究补充了生物素-链霉亲和素的早期工作，采用了更大的谐波力常数，模拟揭示了各种解结合途径，关键残基的作用，有助于粘附以及亲和素结合生物素的空间范围。与以前的研究相比，计算的破裂力远远超过观察到的。我们证明，在模型的框架内表示的一维朗之万方程与示意性的结合势，相关的Smoluchowski方程，和理论的第一次通过时间，皮秒到纳秒的模拟配体解结合需要这样强大的力量，所产生的蛋白质配体运动的收益远远从热激活制度的毫秒AFM实验，并且模拟的松解不能容易地外推到实验观察到的破裂。
We report molecular dynamics simulations that induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force constants close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force constant, The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calculated rupture forces exceed by far those observed. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the associated Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM experiments, and that simulated unbinding cannot be readily extrapolated to the experimentally observed rupture.