Computation & Chemistry Core

计算

基本信息

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
项目类别：
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

项目摘要

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