Core 2 - Computational Biology Core

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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.