Core A Computational Core

核心A 计算核心

• 批准号: 10471370
• 负责人: CAMERON F ABRAMS
• 金额: $ 13.62万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471370
• 关键词: 3-Dimensional; Algorithms; Binding; CD4 Antigens; Cells; Complex; Consultations; Custom; Databases; Docking; Drug Design; Evaluation; Free Energy; Generations; Glycoproteins; HIV Envelope Protein gp120; HIV-1; Joints; Lead; Mass Spectrum Analysis; Methods; Modeling; Molecular; Molecular Conformation; Molecular Probes; Moths; Participant; Peptides; Preparation; Provider; Sampling; Software Design; Structure; Testing; Triazoles; Work; antagonist; base; crosslink; design; experimental study; flexibility; improved; inhibitor; insight; interest; mimetics; molecular dynamics; molecular modeling; pharmacophore; programs; prospective; protein data bank; screening; simulation; single-molecule FRET; small molecule

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.

核心A：项目摘要 计算核心在整体程序工作流程的多个阶段提供了专业知识 HIV-1 Env机器的新抑制剂产生。该专业知识包括药片 - 基于外部分子数据库的筛选，以产生新的铅分子以及 咨询和基于仿真的评估，对现存的真实套件衍生出的新同类物 该程序已经成功产生的抑制剂。在每种情况下，我们都旨在支持 具有出色活性的新分子的产生，尤其是在HIV-1菌株的广度上，以及 使用3D全原子模型合理化我们的抑制剂与HIV-1信封相互作用的机制 在其各种构象状态中的糖蛋白复合物（ENV）。计算核心采用最新 以及最可靠的计算药物设计软件以及用于目标准备的自定义算法和 基于全原子分子动力学模拟的构象采样。