Computational Core

计算核心 计算核心将通过提供尖端的计算工具来支持三个PCHPI项目， 为PCHPI研究人员提供专业知识，以确定HIV-1复制的结构和动态基础 以原子级的分辨率处理多个尺度。具体目标是：（一）全面 HIV-1与宿主蛋白复合物的胞质转运和核孔的动力学模型 运输，和ii）开发技术，以获得蛋白质-脂质和脂质-脂质相互作用的分子决定因素 在全面的病毒体动力学和现实的脂质组学组成的背景下。计算核心将 设计方法学使用规范分子动力学模拟，增强的采样计算， 自由能计算确定小分子对衣壳蛋白复合物动力学的影响 和集会。原位动力学模型将处理大规模系统，多达十亿个原子。这些创新 方法，结合实验验证，将产生一个完整的原子级模型完整的艾滋病毒- 1病毒体，并提供有关病毒中关键过程的结构和动力学的变革性信息。 复制周期，以指导新的治疗干预措施的发展。

Computational Core The computational core will support the three PCHPI projects by providing cutting-edge computational tools and expertise to PCHPI researchers for determining structural and dynamic bases underlying HIV-1 replication processes across multiple scales, with atomic resolution. Specific aims are designed to: i) derive full-scale dynamic models of HIV-1 and host protein complexes related to HIV-1 cytosolic transport and nuclear pore trafficking, and ii) develop techniques to derive molecular determinants of protein-lipid, and lipid-lipid interactions in the context of full-scale virion dynamics and realistic lipidomic compositions. The computational core will design methodologies using canonical molecular dynamics simulations, enhanced sampling calculations and free energy calculations to determine the effects of small molecules on the dynamics of capsid protein complexes and assemblies. In-situ dynamic models will address large-scale systems, up to a billion atoms. These innovative approaches, in conjunction with experimental validations, will yield a complete atomic-level model of intact HIV- 1 virions and provide transformative information about structures and dynamics of key processes in the viral replication cycle, to guide the development of new therapeutic interventions.