抑制剂8CA与脂肪细胞脂肪酸结合蛋白(A-FABP)结合模式的分子动力学研究  

Insight into binding mode of inhibitor 8CA to A- FABP based on molecular dynamics simulation

作　　者：尹妍妍[1] 梁志强[1] 王伟[1] 伊长虹[1] 李洪云[1] 赵娟[1] 张庆刚[2] 

机构地区：[1]山东交通学院理学院,济南250357 [2]山东师范大学物理与电子科学学院,济南250014

出　　处：《原子与分子物理学报》2016年第2期339-344,共6页Journal of Atomic and Molecular Physics

基　　金：国家自然科学基金(11504206;11274206);山东省高等学校科技计划项目(J14LJ07)

摘　　要：脂肪细胞脂肪酸结合蛋白A-FABP(Adipocyte fatty-acid binding protein)是治疗脂质调节生物过程相关疾病的重要靶标.采用分子动力学模拟和MM-PBSA方法研究抑制剂8CA与A-FABP结合模式,结果表明静电相互作用和范德华作用驱动了抑制剂8CA与A-FABP的结合.基于残基的能量分解表明抑制剂8CA与R126间的极性相互作用为抑制剂与A-FABP的结合提供了重要贡献,该残基与8CA的相互作用较好地稳定了抑制剂与A-FABP复合物的稳定性.期望该研究可为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导.Adipocyte fatty - acid binding protein （ A - FABP） is an important target of drug designs treating some diseases related to lipid - mediated biology. Molecular dynamics （MD） simulations coupled with molecular mechanics Poisson - Bohzmann surface area （ MM - PBSA） calculation were carried out to study the binding mode of 8CA to A - FABP. The results show that electrostatics and van der Waals interactions drive the binding of 8CA to A - FABP. The calculation from residue - based free energy decomposition suggests that the polar in- teraction of 8CA with the residue R126 provides an important contribution to the 8CA binding. This polar interac- tion plays a key role in the stabilization of 8CA/A -FABP complex. We expect that this study can contribute some theoretical guidance for design of potent inhibitors within the fields of metabolic disease, inflammation and atherosclerosis.

关 键 词：分子动力学模拟 MM-PBSA方法 A-FABP 抑制剂-残基相互作用 

分 类 号：Q641.12[生物学—生物物理学]