The analysis of HIV-protease dimerization mechanism at atomic andmolecular resolution, and the design of novel dimerization inhibition compounds.

利用质谱仪和X射线晶体结构分析方法，对HIV-1蛋白水解酶(PR)的二聚化动力学进行了研究。我们的数据显示FDA批准的PR抑制剂达鲁那韦(DR V)可以与PR的单体和二聚体结合，并阻止HIV-1复制。我们还表明，PR中引入了DR V抗性相关氨基酸，阻止了DR V与PR单体的结合，减少了PR二聚体的数量。这些数据不仅在研究PR二聚化动力学方面应该是徒劳的，而且在设计更有效的PR抑制剂方面也应该是徒劳的，这些PR抑制剂几乎不允许出现耐DR V的HIV-1变异株。

Using mass spectrometry and X-ray crystal structure analysis, we attempted toelucidate the dimerization dynamics of HIV -1 protease (PR). Our data showed that darunavir (DR V), anFDA-approved PR inhibitor, binds to both monomers and dimers of PR and blocks HIV -1 replication.We also showed that the introduction of DR V -resistance-associated amino acids into PR prevented DR Vfrom binding to PR monomers and decreased the amount of dimerized PR species. The data should be ofutility in not only examining the PR dimerization dynamics but also designing more potent PR inhibitorsthat hardly permit the emergence of DR V -resistant HIV -1 variants.