AMBER/PBSA: An Open-Source Computer Program for Accurate and Scalable Solvation A

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DESCRIPTION (provided by applicant): The goal of this project is to continue the development and maintenance of the AMBER/PBSA program for the solvation-mediated energetics and dynamics analysis of complex biomolecular systems. Biomolecules normally function in a salt-water environment, which has a strong effect on their structure and function. Water has a dielectric constant of about 80, whereas the dielectric constant of biomolecular interior is as low as 2. This leads to favorable interactions between atomic charges and the high-dielectric water. On the other hand, the high-dielectric water screens or reduces interactions among atomic charges. Water also gives rise to the hydrophobic effect, the tendency of water molecules to drive nonpolar solutes together. This promotes the self-assembly of biomolecules or association of nonpolar surfaces between different biomolecules. These solvation effects are often modeled with the implicit solvation methods for high-performance energetics and dynamics analysis of biomolecules. The widely used AMBER/PBSA program is an open-source computer program for implicit solvation treatments of biomolecules. In this project, we propose to improve the AMBER/PBSA program by incorporating advanced numerical algorithms and expanding its functionalities on readily available serial and parallel computing platforms. We propose to implement novel algorithms to achieve a better balance between accuracy and efficiency, develop new post-analysis methods for more robust modeling of biomolecular dynamics, and explore new dielectric models for more physical treatments of implicit solvation. Finally, we will continue our rigorous validation of implicit solvents and extend software interface to attract more users. 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 a general molecular modeling software for accurate and scalable treatment of solvation. The developed software module will be used to study the relation between structure, dynamics, and function of biomolecules, which is crucial for rational drug design.