Investigating structure activity relationships in autoprocessing by HIV-1 protease

研究 HIV-1 蛋白酶自动加工中的结构活性关系

• 批准号: 10258023
• 负责人: DANIEL N BOLON
• 金额: $ 25.13万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-19 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258023
• 关键词: Affinity; Amino Acids; Antiviral Agents; Antiviral Therapy; Binding; Biological Assay; Biological Models; Biophysics; C-terminal; Chemicals; Chimeric Proteins; Consensus; DNA Binding Domain; Data; Dissociation; Engineering; Ensure; Exhibits; Flow Cytometry; Frequencies; Gel; Goals; HIV-1; HIV-1 protease; Human; Investigation; Knowledge; Learning; Libraries; Life Cycle Stages; Maps; Measures; Mediating; Modeling; Molecular Conformation; Monitor; Mutation; N-terminal; Pattern; Peptide Hydrolases; Point Mutation; Polyproteins; Positioning Attribute; Process; Property; Protease Inhibitor; Reagent; Reporter; Resistance; Resources; Sampling; Site; Structure; Structure-Activity Relationship; Testing; Time; Variant; Viral; Virus; Yeasts; base; design; high throughput analysis; inhibitor/antagonist; insight; mutation screening; next generation sequencing; pathogenic virus; physical property; preference; protein function; transcription factor

Project Summary The long-term goal of this project is a detailed mechanistic understanding of the autoprocessing mechanism by which viral proteases cut themselves out of precursor polyproteins. Autoprocessing is critical to the life cycle of many viruses, but is poorly understood in part because the structure of protease in polyproteins is highly dynamic. In Aim 1, we will determine the potency of a panel of inhibitors for autoprocessing of HIV-1 protease. The results from this aim will provide a guide to understand the physical properties at different positions on inhibitors that govern binding. In Aim 2, we will use deep mutational scanning to determine how all possible point mutations in protease impact autoprocessing efficiency. The results from this aim will determine the physical requirements at each position in protease for autoprocessing. Together, these aims will provide a detailed understanding of the physical underpinnings of autoprocessing by HIV-1 protease.

项目摘要 这个项目的长期目标是对自动处理有一个详细的机械理解 病毒蛋白水解酶将自身从前体多蛋白中分离出来的机制。自动处理是 对许多病毒的生命周期至关重要，但人们对此知之甚少，部分原因是 多聚蛋白中的蛋白水解酶是高度动态的。在目标1中，我们将确定一组 HIV-1蛋白水解酶自动加工的抑制剂。这一目标的结果将为 了解控制结合的抑制剂上不同位置的物理性质。在目标2中，我们 将使用深度突变扫描来确定所有可能的点突变对 自动处理效率。这一目标的结果将决定每个目标的物理需求 在用于自动处理的蛋白酶中定位。总而言之，这些目标将提供对 HIV-1酶自动加工的物理基础。