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 全世界大约有 4000 万人感染了艾滋病毒/艾滋病，但是，保护性疫苗或功能性药物； 尽管经过四十年的深入研究，HIV-1 通过其免疫系统逃避，但治愈方法仍然难以实现。 杜克大学艾滋病病毒结构生物学中心将致力于研究感染和复制过程中的快速结构进化。 HIV-1 包膜 (Env) 蛋白进化的结构研究，以阐明结构功能机制 计算抗逆转录病毒疗法 ART 后的病毒进入、B 细胞和 T 细胞激活以及病毒反弹。 生物学核心（核心 2）将通过提供和开发最先进的技术来支持中心的总体使命 用于询问 HIV-1 进入、B 细胞激活和 HIV-1 动态过程的分子建模工具 其核心将利用分子模拟与潜伏病毒库中的宿主免疫系统相互作用。 跨多个尺度，通过增强的采样方法和序列分析来推进 计算生物学核心的目标是 1) 预测性理解复杂的生物系统。 为蛋白质膜系统提供生物信息学以及常规和增强的采样方法； 考虑聚糖并克服模拟大型蛋白质膜复合物的挑战；3) 确定生物学相关的功能运动。核心中的每个理论家都将与一个或多个项目配对。 成员们同时与核心的其他理论家密切联系，进行协调和实验。 与该核心紧密集成，因为合理的测量设计对于成功至关重要。 通过传播知识、计算工具和资源来实现该中心的目标。 了解所有时间尺度的膜蛋白动力学以及这些时间尺度之间的相互作用 越来越多地被认为是基础和应用生物医学研究的一个关键瓶颈。 高分辨率过程在实验上受到限制，需要一种集成方法，利用可测试的方法 理论方法与先进的结构研究通过将当前的前沿理论方法运用到一个领域。 新的水平，我们将在新的空间和时间水平上实现对 HIV1 和其他病原体的创新研究 解决。