A Novel Computational Method for Diffuse Interface Models of Implicit Solvation of Biomolecules

Georgia Southern University Research And Service Foundation, Inc, Statesboro GA

Investigators

Abstract

In the past two decades, implicit solvent models are of tremendous importance to the biomolecular modeling community with thousands of exemplary applications in the literature due to their low computational cost and relatively high accuracy. The accuracy of implicit solvent models depends on the geometric description of the solute-solvent interface and the solvent dielectric profile that is defined near the molecules. Successful implementations of the proposed model in this project with realistically generated solute-solvent smooth boundaries will greatly improve the accuracy and efficiency of these implicit solvent models. This investigation will be directly integrated into existing implicit solvent software and visualization packages to ensure extensive usages by an established user community of researchers in chemistry, physics, and biology. Moreover, the proposed work will present an unconventional computational method for diffuse interface models applied to spatial multiscale modeling in mathematical biology. Successful development of the proposed work will become a valuable computational tool for studying the transition between regions described by discrete and continuum models. The outcome will have potential impacts across a wide range of scientific fields such as multiscale modeling in cancer research and drug design. The goal of this project is to develop a novel computational method for diffuse interface models of implicit solvation of biomolecules. The computational approach will be mathematically rigorous and computationally efficient to generate physically realistic solute-solvent smooth boundaries by free energy minimization. To this end, an innovative construction is proposed to transform a variational problem subject to bounded admissible functions into an equivalent unconstrained problem so that the traditional Euler-Lagrange Equation can be applied directly. This new computational formulation will be implemented with advanced computational algorithms to ensure their accuracy, stability, and efficiency, and it will be validated by several common biomolecular modeling tasks. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.