Statistical estimation of the protein-ligand binding free energy based on direct protein-ligand interaction obtained by molecular dynamics simulation.
Statistical estimation of the protein-ligand binding free energy based on direct protein-ligand interaction obtained by molecular dynamics simulation.
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DOI：
10.3390/ph5101064
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发表时间：
2012-09-28
期刊：
影响因子：
--
通讯作者：
Nakamura H
中科院分区：
文献类型：
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作者：
Fukunishi Y;Nakamura H
我们发展了一种基于分子动力学模拟得到的蛋白质-配体直接相互作用来估算蛋白质-配体结合自由能（ΔG）的方法。利用该方法，通过计算靶蛋白各氨基酸与配体分子之间的货车范德华力和静电相互作用的平均值，统计估算ΔG值。此外，我们引入了蛋白质-配体复合物体系的可及表面积（阿萨）和二面角的涨落作为ΔG估计的熵项。该方法包括蛋白质结构变化的涨落项和有效介电常数。我们将这种方法应用于34蛋白质-配体复合物结构。结果表明，ΔG的实验值与计算值之间的相关系数为0.81，在固定参数下ΔG的平均误差为1.2kcal/mol。这些结果是从2nsec分子动力学模拟获得的。
We have developed a method for estimating protein-ligand binding free energy (ΔG) based on the direct protein-ligand interaction obtained by a molecular dynamics simulation. Using this method, we estimated the ΔG value statistically by the average values of the van der Waals and electrostatic interactions between each amino acid of the target protein and the ligand molecule. In addition, we introduced fluctuations in the accessible surface area (ASA) and dihedral angles of the protein-ligand complex system as the entropy terms of the ΔG estimation. The present method included the fluctuation term of structural change of the protein and the effective dielectric constant. We applied this method to 34 protein-ligand complex structures. As a result, the correlation coefficient between the experimental and calculated ΔG values was 0.81, and the average error of ΔG was 1.2 kcal/mol with the use of the fixed parameters. These results were obtained from a 2 nsec molecular dynamics simulation.