Solvation is a fundamental process of interactions between solute molecules and solvent or ions in the aqueous environment. Accurate models of solvation are essential prerequisites for the quantitative description and analysis of important biological processes involving the folding, encounter, recognition, and binding of biomolecular assemblies. Solvation models can be roughly divided into two classes: explicit ones that treat the solvent in molecular or atomic detail and implicit solvent models that treat the solvent as a dielectric continuum. Because of their efficiency, implicit solvent models have become very popular for a variety of biological applications, including rational drug design, estimations of folding energies, binding affinities, pKa values, and the analysis of structure, mutation, and many other thermodynamic and kinetic quantities. However, ad hoc assumptions about solvent-solute interfaces are currently used in most implicit solvent models, impeding their reliability, accuracy and efficiency. The proposed project addresses this problem by developing a differential geometry-based multiscale framework. Upon energy minimization, our framework generates the interface between the continuum solvent and the discrete atomistic solute. In particular, variation of the full free energy functional gives rise to selfconsistently coupled geometric and Poisson-Boltzmann equations. The resulting equations will be solved with advanced algorithms. Extensive validations and applications are designed to ensure that the proposed multiscale paradigm yields accurate solvation properties. The importance of implicit solvent models is supported by the thousands of applications in the literature. The proposed research addresses serious limitations in existing models arising from ad hoc assumptions of the solvent-solute interface by the introduction of a new mathematical framework to construct physical interfaces. In total, this proposal offers an innovative approach to an important area in biomolecular modeling .
| Nguyen, Duc D; Wang, Bao; Wei, Guo-Wei (2017) Accurate, robust, and reliable calculations of Poisson-Boltzmann binding energies. J Comput Chem 38:941-948 |
| Wang, Bao; Wei, Guo-Wei (2016) Object-oriented Persistent Homology. J Comput Phys 305:276-299 |
| Opron, Kristopher; Xia, Kelin; Burton, Zach et al. (2016) Flexibility-rigidity index for protein-nucleic acid flexibility and fluctuation analysis. J Comput Chem 37:1283-95 |
| Xia, Kelin; Wei, Guo-Wei (2015) Multidimensional persistence in biomolecular data. J Comput Chem 36:1502-20 |
| Wang, Bao; Xia, Kelin; Wei, Guo-Wei (2015) Second order Method for Solving 3D Elasticity Equations with Complex Interfaces. J Comput Phys 294:405-438 |
| Opron, Kristopher; Xia, Kelin; Wei, Guo-Wei (2015) Communication: Capturing protein multiscale thermal fluctuations. J Chem Phys 142:211101 |
| Xia, Kelin; Wei, Guo-Wei (2015) Persistent topology for cryo-EM data analysis. Int J Numer Method Biomed Eng 31: |
| Wang, Bao; Wei, G W (2015) Parameter optimization in differential geometry based solvation models. J Chem Phys 143:134119 |
| Wang, Bao; Xia, Kelin; Wei, Guo-Wei (2015) Matched Interface and Boundary Method for Elasticity Interface Problems. J Comput Appl Math 285:203-225 |
| Xia, Kelin; Feng, Xin; Tong, Yiying et al. (2015) Persistent homology for the quantitative prediction of fullerene stability. J Comput Chem 36:408-22 |
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