Core 2 - Computational Biology Core

摘要-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，保护性疫苗或功能性疫苗 尽管进行了40年的深入研究，但治愈方法仍然难以捉摸。HIV-1通过其 在感染和复制过程中的快速结构进化。杜克艾滋病毒结构生物学中心将继续研究 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细胞活化以及抗逆转录病毒治疗ART后的病毒反弹。 生物核心（核心2）将通过提供和开发最先进的技术来支持中心的整体使命 用于询问HIV-1进入、B细胞活化和HIV-1的动态过程的分子模拟工具 在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 通过增强的采样方法和序列分析， 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以及常规和增强的采样方法; 2） 解释聚糖并克服模拟大型蛋白质-膜复合物的挑战;以及3） 识别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，而密切相关的其他理论家的核心。实验将得到协调， 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。的能力 了解所有时间尺度上的膜蛋白动力学，这些时间尺度之间的相互作用是 越来越多地被认为是基础和应用生物医学研究的关键瓶颈。访问这些 高分辨率的工艺在实验上是有限的，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。通过采用当前最前沿的理论方法， 新的水平，我们将使创新的研究艾滋病毒1和其他病原体在新的水平的空间和时间 分辨率

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.