Core 2 - Computational Biology Core

抽象-核心2-计算生物学核心 全世界约有4000万人感染艾滋病毒/艾滋病；然而，保护性疫苗或有效的 尽管进行了40年的紧张研究，但治愈方法仍然难以捉摸。HIV-1通过其自身的功能逃避免疫系统 在感染和复制过程中结构的快速演变。杜克大学艾滋病毒结构生物学中心将致力于 HIV-1包膜蛋白进化的结构研究以阐明结构-功能机制 用于病毒进入、B细胞和T细胞的激活，以及抗逆转录病毒治疗后病毒的反弹。计算性 生物核心(核心2)将通过提供和发展最先进的技术来支持中心的总体使命 用于研究HIV-1进入、B细胞激活和HIV-1动态过程的分子模拟工具 潜伏病毒库中与宿主免疫系统的相互作用。核心将利用分子模拟 通过增强的抽样方法和序列分析，在多个范围内推进 对复杂生物系统的预测性理解。计算生物学核心的目标是1) 为蛋白质-膜系统提供生物信息学和常规和改进的采样方法；2) 解释多聚糖并克服模拟大的蛋白质-膜复合体的挑战；以及3) 确定与生物相关的功能运动。核心中的每个理论家将与一个或多个项目配对 成员，同时与核心的其他理论家密切联系。实验将得到协调和 与这一核心紧密结合，因为合理的测量设计是成功的关键。核心将支持 通过传播知识、计算工具和资源来实现中心的目标。有能力 了解所有时间尺度上的膜-蛋白质动力学，以及这些时间尺度之间的相互作用是 越来越被认为是基础和应用生物医学研究的关键瓶颈。访问这些 高分辨率的过程在实验上是有限的，需要一种集成的方法，利用可测试的 理论方法与先进的结构研究。通过将当前的尖端理论方法应用于 在新的水平上，我们将在新的时空水平上对HIV1和其他病原体进行创新研究 决议。

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.