Computation & Chemistry Core

计算

• 批准号: 10650870
• 负责人: Gregory A. Voth
• 金额: $ 164.73万
• 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/10650870
• 关键词: Acceleration; Affinity; Area; Back; Behavior; Binding; Biological; Biological Models; Biotinylation; Capsid; Chemicals; Chemistry; 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; Viral; Work; chemical function; computer studies; computerized tools; design; fitness; information gathering; inhibitor; innovation; interest; kinetic model; model building; models and simulation; molecular dynamics; molecular modeling; multi-scale modeling; nano; 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 Core 1（Voth 和 Forli，负责人）将提供广泛且集成的计算能力，以支持 B-HIVE 项目的科学。 HIV-1 中的许多过程涉及蛋白质、核酸和/或膜 本质上是多尺度的，跨越多个时间和长度尺度，从分子到纳米尺度不等 至介观。因此，在目标 1 中，将开发自下而上的多尺度计算方法，并 实现了 HIV-1 生命周期中许多蛋白质组装过程的特征。才能更深入地了解 详细描述了驱动 HIV 蛋白与宿主因子大分子相互作用的具体物理机制 和核酸，在 Aim 2 全原子分子动力学模拟中，以及蛋白质-蛋白质对接和 动力学模型将用于建立 HIV 蛋白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来分析 兴趣，Aim 3 将提供完善的计算工具和方法，这些工具和方法也将得到进一步开发 并延长。所有三个目标相辅相成，每个目标都将为另一个目标提供重要的投入 以整合的方式实现两个目标。总体而言，Core 1将扩展和开发一套强大的计算工具 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 社区及其他领域。 1