Chen Changjun, Huang Yanzhao, Jiang Xuewei, Xiao Yi
Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China.
Phys Rev E Stat Nonlin Soft Matter Phys. 2013 Jun;87(6):062705. doi: 10.1103/PhysRevE.87.062705. Epub 2013 Jun 14.
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.
结合自由能是描述受体-配体复合物结合亲和力的最重要物理参数。传统上，它是基于热力学循环或炼金术反应获得的。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发生大的构象变化，它们就会出现问题。在本文中，我们提出了一种计算结合自由能的方法：沿着片段化和高维过渡路径的约束动力学。该方法在模拟中直接考虑未结合状态。应用于钙调蛋白环-钙复合物表明该方法是可行的，计算得到的相对结合亲和力与实验结果吻合良好。
