Nakata Hiroya, Fedorov Dmitri G
Department of Fundamental Technology Research, R and D Center Kagoshima, Kyocera , 1-4 Kokubu Yamashita-cho, Kirishima-shi, Kagoshima 899-4312, Japan.
Research Center for Computational Design of Advanced Functional Materials, National Institute of Advanced Industrial Science and Technology , 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
J Phys Chem A. 2016 Dec 15;120(49):9794-9804. doi: 10.1021/acs.jpca.6b09743. Epub 2016 Dec 2.
The analytic gradient is derived for the frozen domain formulation of the fragment molecular orbital (FMO) method combined with the polarizable continuum model. The accuracy is tested in comparison to full FMO calculations for a representative set of systems in terms of the gradient accuracy, protein-ligand binding energies, and optimized structures. The frozen domain method reproduced geometries optimized with full FMO within 0.03-0.09 Å in terms of reduced mean square deviations, whereas a single-point gradient calculation is accelerated by the factor of 38 (Trp-cage protein in explicit solvent, PDB: 1L2Y ) and 12 (crambin, PDB: 1CRN ). The method is applied to a geometry optimization of the K-Ras protein-ligand complex (4Q03) using two domain definitions, and the optimized structures are consistent with experiment. Pair interaction analysis is used to identify residues important in binding the ligand.
推导了结合可极化连续介质模型的片段分子轨道（FMO）方法的冻结域公式的解析梯度。在梯度精度、蛋白质-配体结合能和优化结构方面，与一组代表性体系的全FMO计算结果相比，测试了该方法的准确性。就均方根偏差而言，冻结域方法重现了用全FMO优化的几何结构，偏差在0.03-0.09 Å范围内，而单点梯度计算加速了38倍（在显式溶剂中的色氨酸笼蛋白，PDB：1L2Y）和12倍（胰凝乳蛋白酶原，PDB：1CRN）。该方法应用于使用两种域定义对K-Ras蛋白-配体复合物（4Q03）进行几何优化，优化后的结构与实验结果一致。使用对相互作用分析来识别在结合配体中起重要作用的残基。
