Binding free-energy calculation of an ion-peptide complex by constrained dynamics.
Binding free-energy calculation of an ion-peptide complex by constrained dynamics.
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DOI：
10.1103/physreve.87.062705
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Changjun Chen;Yanzhao Huang;Xuewei Jiang;Yi Xiao
中科院分区：
文献类型：
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作者：
Changjun Chen;Yanzhao Huang;Xuewei Jiang;Yi Xiao
结合自由能是描述受体-配体复合物结合亲和力的最重要的物理参数。常规上，都是通过热力学循环或者炼金反应来获得。这些策略已被广泛使用，但如果受体和/或配体在结合过程中具有大的构象变化，则它们将是有问题的。本文提出了一种计算结合自由能的方法：沿着碎片和高维跃迁路径的约束动力学，这种方法在模拟中直接考虑了未结合态。应用于钙调素环-钙复合物的计算表明，该方法是可行的，计算的相对结合亲和力与实验结果符合得很好。
Binding free energy is the most important physical parameter that describes the binding affinity of a receptor-ligand complex. Conventionally, it was obtained based on the thermodynamic cycle or alchemical reaction. These strategies have been widely used, but they would be problematic if the receptors and/or ligands have large conformational changes during the binding processes. In this paper, we present a way to calculate the binding free energy: constrained dynamics along a fragmental and high-dimensional transition path. This method directly considers unbound states in the simulation. The application to the calmodulin loop-calcium complexes shows that it is practical and the calculated relative binding affinities are in good agreement with experimental results.