物理化学学报2009，Vol.25Issue(4)：668-676,9.
新型二氟甲基磷酸类酪氨酸蛋白磷酸酯酶1B抑制剂的分子动力学模拟和结合自由能计算
Molecular Dynamics Simulations and Free Energy Calculations of a Novel Series of Protein Tyrosine Phosphatase 1B Difluoromethylenephosphonic Acid Inhibitors
摘要
Abstract
Binding models for a series of difluoromethylenephosphonic(DFMP)and difluoromethylenesulfonic (DFMS)acids to protein tyrosine phosphatase 1B(PTP1 B)were studied by molecular docking,molecular dynamics(MD) simulations,and free energy calculations.Binding free energies were computed using the molecular mechanics/generalized Born surface area(MM/GBSA) methodology based on l ns MD simulations.The order of affinities for the studied inhibitors can be accurately predicted using previously predicted binding free energies.Inhibitor/residue interaction profiles for all inhibitors were systematically generated using MM/GBSA free energy decomposition analysis.Inhibitor/residue interaction profiles demonstrated that electrostatic interactions between the negative charge center of DFMP/DFMS groups and Arg221 of PTP1 B are a crucial part of the studied molecule affinities.Furthermore. The fluorine atom or other hydrogen bonding donor atoms with appropriate radii will improve inhibitor binding to the primary binding site of PTPl B.关键词
酪氨酸蛋白磷酸酯酶1B/分子动力学模拟/自由能计算/自由能分解/MM/GBSAKey words
Protein tyrosine phosphatase 1 B/Molecular dynamics simulation/Free energy calculation/Free energy decomposition/MM/GBSA分类
化学化工引用本文复制引用
崔巍,张怀,计明娟..新型二氟甲基磷酸类酪氨酸蛋白磷酸酯酶1B抑制剂的分子动力学模拟和结合自由能计算[J].物理化学学报,2009,25(4):668-676,9.基金项目
国家自然科学基金(20373089)和中国科学院研究生院启动基金(M3004)资助项目 （20373089）
