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首页> 外文期刊>RSC Advances >Structural insights into HIV-1 protease flap opening processes and key intermediates
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Structural insights into HIV-1 protease flap opening processes and key intermediates

机译：对HIV-1蛋白酶皮瓣开放过程和关键中间体的结构见解

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HIV-1 protease (PR) is an effective drug target for antiviral inhibitors. The conformational dynamics in the flaps of HIV-1 PR plays a crucial role in the mechanism of substrate binding. Here, the structural properties of the functionally important intermediate states of the flap opening transition of HIV-1 PR have been characterized by enhanced sampling molecular dynamics simulation as well as long-time conventional non-enhanced simulations at atomic level. Not only crystallographically measured “closed” and “semi-open” structures but also a novel “curled” structure of HIV-1 PR is captured by both kinds of simulations qualitatively and quantitatively. The observation of the “curled” intermediate state helps to connect all other functionally important states to provide an integrated view of the transition pathway of the flap opening of HIV-1 PR (closed → curled → semi-open → fully open). The key residue–residue interactions which are broken or formed in the transition are analyzed to reveal the inherent driving force for the protein conformational transition.
机译：HIV-1蛋白酶（PR）是抗病毒抑制剂的有效药物靶标。 HIV-1 PR皮瓣中的构象动力学在底物结合机制中起着至关重要的作用。在这里，HIV-1 PR的襟翼打开过渡的功能上重要的中间状态的结构特性已经通过增强的采样分子动力学模拟以及在原子水平上的长期常规非增强模拟得到了表征。不仅通过晶体学测量的“封闭”和“半开放”结构，而且通过定性和定量两种模拟，都可以捕捉到HIV-1 PR的新颖“卷曲”结构。对“卷曲的”中间状态的观察有助于将所有其他功能上重要的状态联系起来，以提供HIV-1 PR的皮瓣开口过渡路径的完整视图（闭合→卷曲→半打开→完全打开）。分析了在过渡过程中断裂或形成的关键残基-残基相互作用，以揭示蛋白质构象过渡的内在驱动力。

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