Development of polarizable Gaussian multipole force field for biomolecular simulations based on in-solution electrostatics

About This Grant

Project Summary Physics-based molecular modeling methods have played important roles in biochemical and biophysical sciences. This investigator has led a team of investigators in the development of Amber polarizable force fields with long-term goals to develop force fields that can reproduce biological structure, dynamics and interactions without sacrificing the computational efficiency necessary to reach biologically relevant temporal and size scales. Furthering the advances, this investigator proposes to develop parameters and simulation methodologies that are part of the foundation of molecular simulation platform to push the “Amber” polarizable force field efforts to the next level. A key focus is to not only develop general, reliable and widely applicable polarizable force fields for proteins, nucleic acids and drug-like molecules, but to validate the force fields via vigorous testing using experimental and high-level quantum mechanical data on a variety of molecular systems and at all stages of the development. This proposal is broad reaching in that successes will have positive impact in broad range of scientific and technological areas. The proposed work is broadly categorized in the following areas: 1) Development of polarizable force fields, including parameterization of charges, permanent dipoles, van der Waals and torsion potentials; 2) Critical validation and refinement of polarizable force field parameters for non-trivial model systems; 3) Development of a continuum solvent method for polarizable force fields for efficient calculations of binding free energies; 4) Develop novel methods for improved modeling of charge transfer and atomic quadrupoles.