Developing Fast and Accurate Water Models for Atomistic Molecular Dynamics Simulations

• Main Author: Xiong, Yeyue
• Other Authors: Engineering Science and Mechanics
• Format: Others
• Published: Virginia Tech 2021
• Subjects: water model; molecular dynamics; global optimization; polarizable; Drude
• Online Access: http://hdl.handle.net/10919/105002

Water models are of great importance for different fields of studies such as fluid mechanics, nano materials, and biomolecule simulations. In this dissertation, we focus on the water models applied in atomistic simulations, including those of biomolecules such as proteins and DNA. Despite water's simple structure and countless studies carried out over the decades, the best water models are still far from perfect. Water models are normally divided into two types--explicit model and implicit model. Here my research is mainly focused on explicit models. In explicit water models, fixed charge n-point models are most widely used in atomistic simulations, but have known accuracy drawbacks. Increasing the number of point charges, as well as adding electronic polarizability, are two common strategies for accuracy improvements. Both strategies come at considerable computational cost, which weighs heavily against modest possible accuracy improvements in practical simulations. With a careful comparison between the two strategies, results show that adding polarizability is a more favorable path to take. Optimal point charge approximation (OPCA) method is then applied along with a novel global optimization process, leading to a new polarizable water model OPC3-pol that can reproduce bulk liquid properties of water accurately and run at a speed comparable to 3- and 4-point non-polarizable water models. For practical use, OPC3-pol works with existing non-polarizable AMBER force fields for simulations of globular protein or DNA. In addition, for intrinsically disordered protein simulations, OPC3-pol fixes the over-compactness problem of the previous generation non-polarizable water models. === Doctor of Philosophy === With the rapid advancements of computer technologies, computer simulation has become increasingly popular in biochemistry research fields. Simulations of microscopic substances that are vital for living creatures such as proteins and DNAs have brought us more and more insights into their structures and functions. Because of the fact that almost all the microscopic substances are immersed in water no matter they are in a human body, a plant, or in bacteria, accurately simulating water is crucial for the success of such simulations. My research is focused on developing accurate and fast water models that can be used by researchers in their biochemical simulations. One particular challenge is that water in nature is very flexible and properties of water can change drastically when its surroundings change. Many classical water models cannot correctly mimic this flexibility, and some more advanced water models that are able to mimic it can cost several times more computing resources. Our latest water model OPC3-pol, benefited from a new design, accurately mimics the flexibility and runs as fast as a traditional rigid water model.