Core A Computational Core

核心A：项目总结 计算核心在整个计划工作流程的几个阶段提供专业知识， 产生新的和改进的HIV-1 Env机器抑制剂。该专业知识包括药效团- 基于外部分子数据库的筛选，以产生新的目标先导分子，以及 咨询和基于模拟的评估新的同源物从现有的一套真实的 该计划已成功生成的抑制剂。在每一种情况下，我们的目标都是支持 产生具有上级活性的新分子，特别是在跨越HIV-1毒株的广度方面， 用3D全原子模型合理化我们的抑制剂与HIV-1包膜相互作用的机制 糖蛋白复合物（Env）以其各种构象状态存在。计算核心采用最新的 最可靠的计算药物设计软件以及用于靶向制备的定制算法， 基于全原子分子动力学模拟的构象采样。

Core A: PROJECT SUMMARY The Computational Core provides expertise at several stages of the overall Program workflow aimed at the generation of new and improved inhibitors of the HIV-1 Env machine. This expertise includes pharmacophore- based screening of external molecule databases to generate new lead molecules of interest, as well as consultation and simulation-based evaluation of new congeners derived from the extant set of authentic inhibitors already successfully generated by the Program. In each of these cases, we aim both to support the generation of new molecules with superior activity, especially in terms of breadth across HIV-1 strains, and to rationalize with 3D all-atom models the mechanisms by which our inhibitors interact with the HIV-1 envelope glycoprotein complex (Env) in its various conformational states. The Computational Core employs the latest and most reliable computational drug design software as well as custom algorithms for target preparation and conformational sampling based on all-atom molecular dynamics simulations.