同源建模
对接(动物)
分子动力学
化学
生物物理学
计算生物学
机制(生物学)
分子模型
生物化学
立体化学
生物
计算化学
酶
物理
医学
量子力学
护理部
作者
Leilei Liang,Qing‐Chuan Zheng
摘要
α-Tocopherol (α-TOH) is a potent antioxidant. The concentrations of α-TOH in plasma are closely related to human health. α-TOH can be regulated by the metabolism of cytochrome P450 4F2 (CYP4F2). However, the atomic-level basis for this regulation process remains elusive. Here, we successfully constructed the structure of CYP4F2 by homology modeling and obtained the α-TOH-CYP4F2 complex models using molecular docking. Three parallel 500 ns molecular dynamics simulations were performed on each complex model to investigate the details of the interaction between α-TOH and CYP4F2. MM-GBSA method combined with principal component analysis shows that 8 key residues establish a hydrophobic cavity stabilizing α-TOH in the pocket of CYP4F2 and S423 forms an important hydrogen bond with α-TOH anchoring α-TOH in the favorable position for ω-hydroxylation. Based on our simulation results and the experimental facts, we designed mutation simulation experiments to clarify the important role of two key residues (S423 and V433) in the binding of α-TOH with CYP4F2. The results show that the mutations directly or indirectly change the binding mode of α-TOH and decrease its binding affinity with CYP4F2, which is unfavorable for ω-hydroxylation. Our results could enrich the information on structure-function relationships of CYP4F2 and provide valuable insights into the regulatory mechanism of CYP4F2 on the metabolism of α-TOH.
科研通智能强力驱动
Strongly Powered by AbleSci AI