Free energy perturbation calculations on multiple mutation bases-猫眼课题宝

多个突变碱基的自由能扰动计算

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1992

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作者：

S. Yoneda;H. Umeyama

本文提出了一种在自由能微扰计算中使用多个势函数（突变基）的新方法，使突变途径更加有效。该方法，这是一个推广的传统的耦合参数的方法，允许更多的自由度和光滑的曲线形状的路径被生产。用该方法对64个四原子分子组成的模型系统在周期性边界条件下进行了分子动力学模拟，得到了相对自由能。五个突变途径的有效性进行了比较，使用所得的自由能值和最终的transconformations的比率。为了提高置信度，对每个突变途径的形状和长度进行了15次自由能微扰计算，并计算了平均值和标准误差。结果表明，其中一种途径（如果没有多个突变碱基，则不可能）比Mark等人[J. Chem. Phys. 94，3808（1991）]提出的缩小规模的途径更有效，并且比常规偶联参数方法的简单突变有效得多。

A new method of using multiple potential functions (mutation bases) in free energyperturbation calculations is proposed to make more effective mutation pathways. The method, which is a generalization of the conventional coupling parameter approach, allows pathways of more freedom and of smoothly curved shapes to be produced. Molecular dynamics simulations were carried out by the method to derive relative free energy on a model system made of 64 four‐atom molecules in the periodic boundary condition. Effectiveness of five mutation pathways was compared using the resulting free energy values and the final ratios of transconformations. For confidence, 15 free energyperturbation calculations were carried out for each shape and length of the mutation pathways, and means and standard errors were calculated. Results showed that one of the pathways, which is impossible without the multiple mutation bases, is more effective than the down‐scaled pathway proposed by Mark et al. [J. Chem. Phys. 94, 3808 (1991)], and is much more effective than the simple mutation of the conventional coupling parameter approach.

Toward computer-aided site-directed mutagenesis of enzymes.