DESCRIPTION (provided by applicant): Atomistic simulations of biomolecules provide a detailed view of structure and dynamics that complement experiments. Increased conformational sampling, enabled by new algorithms and growth in computer power, now allows a much broader range of events to be observed, providing critical insights, largely inaccessible to experiments. Advancements in implicit solvation treatments have furthered the simulation reach to a broader range of studies of biomolecular structure, dynamics and function, including protein folding and misfolding, protein structure prediction, protein-ligand binding, enzyme mechanisms, and drug design. The AMBER/PBSA program is an open-source computer program for implicit solvation modeling of biomolecules. In this project, we propose to continue the maintenance and improvement of the AMBER/PBSA program by (1) growing and improving the AMBER/PBSA program in response to suggestions by our users; (2) developing and integrating lightweight analysis tools to facilitate better molecular simulations; (3) developing dielectric model for complex systems without apparent solvent/solute interface; and (4) continuing to validate the PB models.

PUBLIC HEALTH RELEVANCE: Solvation plays an important role in all basic biomolecular events and therefore is integral to the modeling of biomolecular structure and function. This application intends to continue the development of the AMBER/PBSA program, a pivotal program for modeling biomolecular solvation in the community, as attested by the approximately 1,500 citations per year to our development efforts and software in the last five years. Having assisted biomedical researchers in computational investigations of protein/nucleic acid-ligand interactions, protein/nucleic acid folding, drug discovery and design, and many other important questions, the AMBER/PBSA program will be extended in its existing functionalities and supports of new models for more robust and accurate solvation modeling to ensure its ongoing availability for biomedical researchers.