Abstract

This dissertation explores the development of a physics-based force field meticulously tailored to guide molecular dynamics simulations of biomolecules. At its core, the Hydrogen-like Intermolecular Polarizable Potential (HIPPO) force field emerges as an apex of achievement, devised to refine the precision of short-range intermolecular interactions. HIPPO's inception marks a profound stride towards heightened realism in molecular simulations, anchored in Quantum Physics theory and fortified by state-of-the-art Quantum Chemistry calculations. This force field's efficacy is attested by its systematic application in constructing models featuring diverse organic molecules, from water to benzene, and those with motifs resembling proteins and nucleic acids. HIPPO achieves an accuracy of 1 kcal/mol for each of its energy components of electrostatic, induction, repulsion, and dispersion when compared against ab initio Symmetry Adapted Perturbation Theory calculations while exhibiting striking conformity with an array of experimental bulk phase properties. HIPPO performs this without imposing a significant computational burden, thus positioning it comparably to the widely used AMOEBA force field.

Committee Chair

Jay Ponder

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Computational & Molecular Biophysics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

12-19-2023

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-7550-6039

Included in

Biology Commons

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