HIV-1蛋白酶与其抑制剂相互作用的分子动力学研究

摘要

Objective: To investigate the molecular recognition mechanism of HIV-1 protease with inhibitor ritonavir. Methods: A 4 nsmolecular dynamics simulation of HIV-1 protease-ritonavir complex and HIV-1 protease were carried out. Results: Ritonavir did nothave significant effect on the backbone movement of HIV-1 protease. It could form stable hydrogen bonds with Ile50, Asp 128 andAspl29 of HIV-1 protease. Ritonavir could exhibit strong interaction with Asp25, Ala28, Asp29, Gly49, Ile50, Aspl24, Aspl28, Aspl29,Glyl48, Ilel49, Val181 and Ilel83. Conclusion: HIV-1 protease could recognize ritonavir through the above 12 residues' non-bondedinteractions.%目的:研究抑制剂利托那韦与HIV-1蛋白酶相互作用的分子识别机制.方法:利用HIV-1蛋白酶与利托那韦晶体结构复合物和HIV-1蛋白酶晶体结构进行4 ns的分子动力学模拟.结果:利托那韦对HIV-1蛋白酶骨架运动影响不大,与HIV-1蛋白酶Ile50、Asp128和Asp129形成稳定氢键作用.利托那韦与Asp25、Ala28、Asp29、Gly49、Ile50、Asp124、Asp128、Asp129、Gly148、Ile 149、Val181和Ile183总相互作用能均较大.结论:HIV-1蛋白酶通过上述12个残基的非价键作用对利托那韦进行生物识别.