Abstract:

This dissertation develops a Gaussian-density alternative to the conventional point-charge + Lennard–Jones decomposition of nonbonded interactions in biomolecular force fields, along three physical pillars: polarizable Gaussian multipole (pGM) electrostatics with explicit induction; the double exponential van der Waals form as well as derived dispersion damping; and applications to water models and alchemical free-energy calculations. Contributions include an isotropic-periodic-sum extension of pGM that matches particle-mesh Ewald, algorithms that resolve the energy-conservation problem in induced-dipole models, MPI-parallel and CUDA implementations in AMBER, a DEGAUSS three-point rigid water model, the self-consistent Gaussian van der Waals (GVDW) potential, and alchemical free-energy calculations on the bounded DEGAUSS Hamiltonian. Together these contributions reorganize the empirical nonbonded partition along natural physical lines, each emerging from a single physical move: replacing the delta-function atomic density with a Gaussian of finite width.