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

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In the past two decades, implicit solvent models are of tremendous importance to the biomolecularmodeling community with thousands of exemplary applications in the literature due to their lowcomputational cost and relatively high accuracy. The accuracy of implicit solvent models dependson the geometric description of the solute-solvent interface and the solvent dielectric profile thatis defined near the molecules. Successful implementations of the proposed model in this project withrealistically generated solute-solvent smooth boundaries will greatly improve the accuracy andefficiency of these implicit solvent models. This investigation will be directly integrated into existingimplicit solvent software and visualization packages to ensure extensive usages by an establisheduser 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 computationaltool 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 multiscalemodeling in cancer research and drug design. The goal of this project is to develop a novel computational method for diffuse interface models ofimplicit solvation of biomolecules. The computational approach will be mathematically rigorous andcomputationally efficient to generate physically realistic solute-solvent smooth boundaries by freeenergy minimization. To this end, an innovative construction is proposed to transform a variationalproblem subject to bounded admissible functions into an equivalent unconstrained problem sothat the traditional Euler-Lagrange Equation can be applied directly. This new computationalformulation 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.