HIV-1逆转录酶非核苷类抑制剂MKC分子结合位点的理论研究

A Theoretical Study of Non-nucleoside Inhibitor MKC Molecular Binding Sites at the HIV-1 Reverse Transcriptase

1RT1蛋白是一个HIV-1逆转录酶核心蛋白,是抑制剂药物分子的作用靶点.非核苷类抑制剂MKC分子是1RT1蛋白中的配体分子.采用量子力学密度泛函理论,B3LYP计算方法,结合6-31G(d,p)基组,逐个计算MKC分子与其周围半径0.7 nm结构范围内的34个氨基酸残基相互作用和结合能,发现在1RT1蛋白中103Lys残基是MKC分子的结合作用位点,结合能值为-46.73 kJ.mol-1.该结合位点的发现将为进一步设计和寻找抗HIV-1逆转录酶抑制剂药物分子提供一些理论基础.

1RT1 protein is a core -structure protein of HIV-1 reverse transeriptase, which is a target to be used for controlling Aids by non-nucleoside inhibitors. The MKC molecule, a non-nucleoside inhibitor, is a ligand molecule extracted from 1 RT1 protein. The paper adopts the B3LYP/6-31 G（d, p） method to explore the interaction and binding energies between MKC molecule and every single of 34 amino acid residues arranged in the sphere of 0.7nm radius around MKC molecule. The results obtained indicate that 103Lys residue is a binding site of 1RT1 protein for MKC molecule with its binding energy of -46.73kJ·mol^-1. The proved binding site will help provide some theoretical foundation to explore and design the HIV-1 reverse transcriptase inhibitor drug molecules.