Structure and Computational Modeling

结构和计算建模

• 批准号: 7434200
• 负责人: DAVID S GOODSELL
• 金额: $ 19.41万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-18 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7434200
• 关键词: Binding; Complex; Computer Analysis; Computer Simulation; Docking; Drug Design; Drug Interactions; Drug resistance; Endopeptidases; Enzymes; Evolution; HIV Protease; HIV-1 protease; Individual; Modeling; Molecular; Peptide Hydrolases; Proteins; Screening procedure; Services; Structural Models; Structure; Techniques; Variant; base; computer studies; inhibitor/antagonist; molecular modeling; mutant; programs; small molecule; virtual

Understanding the evolution of drug resistance in HIV-1 protease necessitates a molecular-level description of protein variants and small molecule (drug) interactions. The Structure and Modeling Core will provide structural information for retroviral proteases and their small molecule complexes as required by the four Projects. The Core will perform service-oriented structural and computational studies, using proven techniques of x-ray crystallographic analysis, computational docking, and rational drug design. Dr. Goodsell will direct the structural modeling and docking analysis of mutant enzymes and their complexes, based on crystal structures and extending analysis to all mutants and potential inhibitors as identified in the individual Projects. Dr. Stout will direct the crystallographic structure determination of retroviral proteases and their complexes.

了解HIV-1蛋白酶中耐药性的演变需要分子级 蛋白质变异和小分子（药物）相互作用的描述。结构和建模核心将 提供逆转录病毒蛋白酶及其小分子复合物的结构信息 四个项目。核心将使用经过验证的 X射线晶体学分析，计算对接和合理药物设计的技术。 Goodsell博士 将基于突变酶及其复合物的结构建模和对接分析 晶体结构并将分析扩展到所有突变体和潜在抑制剂 项目。 Stout博士将指导逆转录病毒蛋白酶的晶体结构确定 复合物。