Potential of mean force calculations of ligand binding to ion channels from Jarzynski's equality and umbrella sampling
Potential of mean force calculations of ligand binding to ion channels from Jarzynski's equality and umbrella sampling
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DOI：
10.1063/1.2904461
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发表时间：
2008-04-21
影响因子：
4.4
通讯作者：
Kuyucak, Serdar
中科院分区：
文献类型：
--
作者：
Bastug, Turgut;Chen, Po-Chia;Kuyucak, Serdar
平均力势（PMF）计算为确定蛋白质-配体系统的绝对结合自由能提供了一种可靠的方法。常用的方法是采用带加权直方图分析的伞形采样法，计算量大，限制了其应用。最近，一个更简单的替代PMF计算已经成为可能，即使用Jarzynski的平等在操纵分子动力学模拟。到目前为止，已经有一些比较这两种方法，主要是在简单的系统，不反映蛋白质配体系统的复杂性。在这里，我们使用这两种方法来计算离子渗透和配体结合到离子通道的PMF。比较结果表明，Jarzynski的方法遭受松弛问题，在复杂的系统，将需要更长的模拟时间，以产生可靠的PMF蛋白质配体系统。(C)2008年美国物理学会。
Potential of mean force (PMF) calculations provide a reliable method for determination of the absolute binding free energies for protein-ligand systems. The common method used for this purpose-umbrella sampling with weighted histogram analysis-is computationally very laborious, which limits its applications. Recently, a much simpler alternative for PMF calculations has become available, namely, using Jarzynski's equality in steered molecular dynamics simulations. So far, there have been a few comparisons of the two methods and mostly in simple systems that do not reflect the complexities of protein-ligand systems. Here, we use both methods to calculate the PMF for ion permeation and ligand binding to ion channels. Comparison of results indicate that Jarzynski's method suffers from relaxation problems in complex systems and would require much longer simulation times to yield reliable PMFs for protein-ligand systems. (C) 2008 American Institute of Physics.