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

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. 分子动力学模拟和MM-PBSA方法被采用研究抑制剂8CA与A-FABP结合模式. 研究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. 我们期望这个研究能为治疗炎症、动脉硬化和代谢病药物设计提供一定的理论指导。

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

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.