HIV感染宿主细胞的关键一步是其囊膜糖蛋白gp120和gp41诱导的细胞膜融合过程，因此它们是当今设计抗HIV抑制剂和疫苗的重要药物靶点和抗原前体。然而人们对gp120-gp41复合物在与其受体和共受体结合后诱导的构象变化过程还缺乏分子水平上的深入理解。本项目计划利用高性能计算的工具，通过计算机模拟的方法和构建马尔科夫态模型的手段对CD4诱导的gp120单体和三聚体的动态变化过程及gp41的自折叠机理进行系统的理论研究，并最终揭示HIV囊膜糖蛋白在诱导膜融合过程中的关键中间体构象及相应的热力学和动力学特性。最终，捕捉到的关键中间体可以作为设计高效和全新抗HIV药物小分子的潜在药物靶点，并为设计具有可诱导广谱中和抗体特性的HIV疫苗提供新的思路。

During the HIV entry, membrane fusion of the HIV and host cells is the first step and driven mainly by the glycoproteins gp120 and gp41 that form a trimer on the surface of the HIV envelope. Therefore, the gp120-gp41 complex is an important drug target to design HIV inhibitors and precursors for the HIV vaccine. However, the underlying mechanisms and atomistic-level understandings of the conformational changes of the gp120-gp41 complex induced by its receptor CD4 and co-receptors CCR5 or CXCR4 are still lack of. In current project, we are focused on investigating the dynamics of the gp120 in both its monomer and trimer state after its binding to CD4 and the refolding mechanisms of the gp41 by combining with high throughput computing, molecular dynamics simulations and Markov State Model (MSM). We expect to capture the key intermediate state of both gp120 and gp41, as well as their associated thermodynamic and kinetic properties. Finally, the above observed intermediate states can be used as potential drug targets for future structure-based anti-HIV drug discovery to design new-scaffold HIV inhibitors with high antivirus activities. In addition, our results will provide new insights for designing novel HIV vaccines that is capable of eliciting broadly neutralizing antibodies.