Core 2 - Computational Biology Core

核心 2 - 计算生物学核心

• 批准号: 10506665
• 负责人: Rory Henderson
• 金额: $ 66.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-14 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506665
• 关键词: AIDS/HIV problem; Accounting; Antibodies; Antibody Response; B-Cell Activation; B-Lymphocytes; Back; Binding; Bioinformatics; Cells; Chemistry; Communities; Complex; Computational Biology; Data; Databases; Development; Dimensions; Educational workshop; Evolution; Experimental Designs; Goals; Grain; HIV; HIV-1; Immune system; Individual; Infection; Intuition; Knowledge; Lipids; Measurement; Membrane; Membrane Proteins; Methods; Mission; Modeling; Molecular; Motion; Mutation; Persons; Polysaccharides; Process; Protein Dynamics; Protein Engineering; Reaction; Research; Resolution; Sampling; Sampling Errors; Sequence Analysis; Structure; Structure-Activity Relationship; System; T-Cell Activation; Techniques; Vaccines; Viral; Viral reservoir; Virus Latency; antiretroviral therapy; applied biomedical research; complex biological systems; computerized tools; computing resources; conformational conversion; env Gene Products; expectation; experimental study; glycosylation; graph theory; improved; innovation; member; molecular dynamics; molecular modeling; novel strategies; open source; pathogen; rational design; simulation; structural biology; success; temporal measurement; tool; viral rebound

Abstract – Core 2 – Computational Biology Core Approximately 40 million people worldwide are living with HIV/AIDS; however, a protective vaccine or functional cure remain elusive despite four decades of intense research. HIV-1 evades the immune system through its rapid structural evolution during infection and replication. The Duke Center for HIV Structural Biology will pursue structural studies of the evolution of the HIV-1 Envelope (Env) protein to elucidate structure-function mechanisms for viral entry, B-cell and T-cell activation, and viral rebound after antiretroviral therapy ART. The Computational Biology Core (Core 2) will support the overall mission of the Center by providing and developing state of the art molecular modelling tools for interrogating dynamic processes in HIV-1 entry, B-cell activation and HIV-1 interactions with the host immune system in latent viral reservoirs. The core will leverage molecular simulations across multiple scales with enhanced sampling approaches and sequence analysis towards advancement of predictive understanding of complex biological systems. The aims of the computational Biology core are 1) to provide bioinformatics and conventional and enhanced sampling methods for protein-membrane systems; 2) to account for glycans and overcome challenges of simulating large protein-membrane complexes; and 3) to identify biologically relevant functional motions. Each theorist in the core will be paired with one or more project members while closely associated with the other theorists in the core. Experimentation will be coordinated and tightly integrated to this core as the rational design of measurements is critical for success. The core will support the aims of the Center by disseminating knowledge and computational tools and resources. The ability to understand membrane-protein dynamics across all timescales and the interplay between these timescales is increasingly recognized as a critical bottleneck in basic and applied biomedical research. Access to these processes at high resolution is limited experimentally necessitating an integrated approach, leveraging testable theoretical methods with advanced structural studies. By taking current cutting-edge theoretical methods to a new level, we will enable innovative studies of HIV1 and other pathogens at a new level of spatial and temporal resolution.

摘要 - 核心2 - 计算生物学核心 全世界约有4000万人患有艾滋病毒/艾滋病；但是，受保护的疫苗或功能 治愈仍然是难以捉摸的任务四十年的深入研究。 HIV-1通过其逃避免疫系统 感染和复制过程中的快速结构演变。杜克大学艾滋病毒结构生物学中心将购买 HIV-1包膜（ENV）蛋白演化以阐明结构功能机理的结构研究 对于病毒输入，B细胞和T细胞激活以及抗逆转录病毒疗法后的病毒反弹。计算 生物学核心（核心2）将通过提供和发展最新状态来支持该中心的整体任务 用于询问HIV-1输入，B细胞激活和HIV-1中动态过程的分子建模工具 潜在病毒储层中与宿主免疫系统的相互作用。核心将利用分子模拟 在多个尺度上，采用增强的采样方法和序列分析朝着进步 对复杂生物系统的预测理解。计算生物学核心的目的是1） 为蛋白质包膜系统提供生物信息学以及常规和增强的采样方法； 2）到 解释了聚糖并克服模拟大型蛋白质膜复合物的挑战；和3）到 确定与生物学相关的功能运动。核心中的每个理论家将与一个或多个项目配对 成员虽然与核心中的其他理论家密切相关。实验将是协调的，并且 紧密整合到该核心，因为测量的合理设计对于成功至关重要。核心将支持 通过传播知识，计算工具和资源的目的。能力 了解所有时间尺度上的膜 - 蛋白质动力学以及这些时间表之间的相互作用是 在基本和应用生物医学研究中，人们越来越被认为是关键瓶颈。访问这些 高分辨率的过程在实验上是有限的，一种集成方法，利用可测试的方法 具有高级结构研究的理论方法。通过将当前的前沿理论方法采用 新级别，我们将在新的空间和临时水平上对HIV1和其他病原体进行创新研究 解决。