Date of Award

6-12-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Pengfei Li

Abstract

Many biological proteins require the presence of a metal ion in order to properly function. However, metal ions’ complex nature charge poses several challenges to accurately and efficiently simulate computationally. For example, metal ions can exhibit multiple oxidation states, electronic state degeneracy, flexible coordination numbers, and significant polarization effects. To address these problems, this dissertation aims to enhance force fields for modeling metal ions in molecular dynamics simulations. First, a comprehensive set of van der Waals radii for metal ions is derived, demonstrating the importance of using physically meaningful parameters in force fields. Second, a comprehensive set of atomic and ionic polarizabilities across the periodic table is established, exploring their relationship with van der Waals radii. These studies lay the foundation for developing a general polarizable force field for metal ions. Third, we developed a strategy to parametrize the C4 parameters in the 12-6-4 model using an energy decomposition approach based on quantum mechanical calculations, exemplified in metal-imidazole systems. Finally, a practical study of a metalloprotein simulations using conventional molecular dynamics and free energy calculations is presented. Overall, this dissertation contributes to the metal-ion modeling community by providing comprehensive sets of polarizabilities and van der Waals radii for ions, contributing to ion-imidazole parameters, and providing key insights into protein-ion binding affinity regulation.

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