基于丙氨酸扫描与相互作用熵方法的PARP1与配体的结合自由能计算

Calculation of PARP1-ligand binding free energy using alanine scanning and interaction entropy method

PARP1蛋白是真核细胞DNA损伤修复的关键因子,也是近年来肿瘤治疗的新热靶标之一.本文运用本课题组发展的基于相互作用熵方法并结合MM/GBSA方法对蛋白-配体进行丙氨酸扫描,计算了10个抑制剂小分子与PARP1蛋白及与PARP1蛋白各残基间的相互作用结合自由能并由此获得总的结合自由能.计算结果表明,相比传统MM/GBSA方法,新的计算方法可以显著提高蛋白-配体结合自由能计算的精度,缩小与实验值的误差.

Poly（ADP-ribose） polymerase 1（PARP1） is a novel target of cancer medication for its important role in DNA repair. In this article, we use interaction entropy（IE） approach combined with the MM/GBSA method to compute residue-specific protein-ligand binding free energies for ten ligands and these residue-specific binding free energies are combined to produce total protein-ligand binding free energy. Our calculated binding free energies are in much better agreement with the corresponding experimental data than those using standard MM/GBSA approach.