Computation & Chemistry Core

计算

• 批准号: 10508446
• 负责人: Gregory A. Voth
• 金额: $ 79.61万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-22 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10508446
• 关键词: Affinity; Area; Back; Behavior; Binding; Biological; Biological Models; Biotinylation; Capsid; Chemicals; Collaborations; Communities; Complement; Computer software; Computing Methodologies; Data; Development; Docking; Ensure; Environment; Event; Foundations; Free Energy; Goals; Grain; HIV; HIV-1; Integration Host Factors; Kinetics; Label; Length; Life Cycle Stages; Machine Learning; Mediating; Membrane; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Molecular Probes; Mutation; Nature; Nucleic Acids; Postdoctoral Fellow; Process; Proteins; Protocols documentation; Research; Research Personnel; Resources; Role; Sampling; Science; Site; Solvents; Speed; Structural Models; Structure; Students; Synthesis Chemistry; Therapeutic; Thermodynamics; Time; Variant; Viral; Work; base; chemical function; computational chemistry; computer studies; computerized tools; design; fitness; inhibitor; innovation; interest; kinetic model; models and simulation; molecular dynamics; molecular modeling; multi-scale modeling; protein protein interaction; rational design; simulation; small molecule; spatiotemporal; tool; training opportunity; virtual; virtual screening

ABSTRACT, CORE 1 Core 1 (Voth and Forli, Leads) will provide an extensive and integrated computational capability in support of the science of the B-HIVE Projects. Many processes in HIV-1 that involve proteins, nucleic acids, and/or membranes are inherently multiscale, spanning multiple time and length scales, which vary from the molecular to nanoscopic to mesoscopic. Therefore, in Aim 1 bottom-up multiscale computational methods will be developed and implemented that characterize many-protein assembly processes in the HIV-1 lifecycle. To understand in greater detail the specific physical mechanisms which drive macromolecular interactions of HIV proteins with host factors and nucleic acids, in Aim 2 all-atom molecular dynamics simulations, together with protein-protein docking and kinetic modeling, will be used to build models of HIV proteins interacting with their partners. In order to support the B-HIVE Projects through computational structure-based pipelines and tools for the analysis of targets of interest, Aim 3 will provide well-established computational tools and methods that will also be further developed and extended. All three Aims complement one another and each Aim will provide important input to the other two Aims in an integrated fashion. Overall, Core 1 will extend and develop a set of powerful computational tools in support of the B-HIVE Projects. The Core will also provide valuable new resources for the overall HIV research community and beyond. 1

摘要，核心1 核心1(Voth和Forli，Leads)将提供广泛和集成的计算能力，以支持 B-HIVE项目的科学。HIV-1中涉及蛋白质、核酸和/或膜的许多过程 本质上是多尺度的，跨越多个时间和长度尺度，从分子到纳米尺度各不相同 到介观。因此，在目标1中，将开发自下而上的多尺度计算方法并 实施了在HIV-1生命周期中描述多种蛋白质组装过程的方法。为了更好地理解 详述驱动HIV蛋白与宿主因子大分子相互作用的特定物理机制 和核酸，在目标2全原子分子动力学模拟中，结合蛋白质-蛋白质对接和 动力学建模，将用于建立艾滋病毒蛋白质与其伴侣相互作用的模型。为了支持 B-HIVE项目通过基于计算结构的管道和工具分析目标 感兴趣的是，AIM 3将提供成熟的计算工具和方法，这些工具和方法也将得到进一步开发 和延展。所有这三个目标是相辅相成的，每个目标都将为另一个目标提供重要的投入 两个目标合而为一。总体而言，Core 1将扩展和开发一组强大的计算工具 以支持B-HIVE项目。该核心还将为整个艾滋病毒研究提供宝贵的新资源 社区和其他地方。 1