Differential geometry based solvation model. I: Eulerian formulation (Q602920)

This paper presents a differential geometry based model for the analysis and computation of the equilibrium property of solvations. The objective is to introduce a differential geometry based approach for the generation of smooth surfaces with good stability and differentiability for use in both polar and nonpolar modeling, thereby addressing many of these current challenges. The authors propose to optimize a polar and nonpolar solvation free energy functional to derive the construction of realistic solvent-solute boundaries and thereby improve the accuracy and stability of implicit solvent calculations. The differential geometry theory of surfaces and manifolds is employed to result in new coupled geometric and potential flows for the generation of a physical solvent-solute boundary and the optimization of solvation energy. Technically, the smoothness of the resulting solute-solvent boundary is ensured by coupled geometric and potential flows of parabolic type. Computational methods and algorithms are constructed and carefully validated to ensure their accuracy, stability, and efficiency. The proposed solute-solvent boundary model and associated free energy functional are tested by their applications in several common biomolecular modeling tasks. The paper is organized as follows: Section 2 is devoted to the theoretical foundations of the present differential geometry based solvation model. A variational framework is established to couple different parts of the solvation contributions. The governing equations are derived by variational principles. The solution of the governing equations leads to physical solvent-solute boundaries and accurate solvation free energies. Numerical methods and algorithms are discussed in Section 3. Schemes of second-order numerical accuracy are designed for the construction and evolution of solute characteristic functions. Appropriate preconditions are used for solving the generalized Poisson-Boltzmann equations. The coupled equations are solved by two iterative schemes. Section 4 presents validation and analysis of the proposed numerical approaches. The accuracy and convergence of various computational schemes, including the surface area formulation based on geometric measure theory, are carefully tested to ensure their computational reliability and efficiency. The applications of the proposed theories, methods and algorithms are considered in Section 5 for two sets of compounds: small molecules and proteins. Comparisons are given with results in the literature.