【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.更多还原

【Abstract】 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- Boltzmann 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 interaction of 8CA with the residue R126 provides an important contribution to the 8CA binding. This polar interaction 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.更多还原