Computational Core

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Computational Core The computational core will support the three PCHPI projects by providing cutting-edge computational tools and expertise to PCHPI researchers for determining structural and dynamic bases underlying HIV-1 replication processes across multiple scales, with atomic resolution. Specific aims are designed to: i) derive full-scale dynamic models of HIV-1 and host protein complexes related to HIV-1 cytosolic transport and nuclear pore trafficking, and ii) develop techniques to derive molecular determinants of protein-lipid, and lipid-lipid interactions in the context of full-scale virion dynamics and realistic lipidomic compositions. The computational core will design methodologies using canonical molecular dynamics simulations, enhanced sampling calculations and free energy calculations to determine the effects of small molecules on the dynamics of capsid protein complexes and assemblies. In-situ dynamic models will address large-scale systems, up to a billion atoms. These innovative approaches, in conjunction with experimental validations, will yield a complete atomic-level model of intact HIV- 1 virions and provide transformative information about structures and dynamics of key processes in the viral replication cycle, to guide the development of new therapeutic interventions.