School of Physics Thesis Dissertation Defense

Presenter:       Yui Tik (Andrew) Pang

Title:                Biomolecules Conformational Changes Studied by Simulations and Enhanced Sampling

Date:               Tuesday, November 7, 2023

Time:               2:00 p.m.   

Place:              Manufacturing Related Disciplines Complex (MRDC), Conference Room 4211

Committee:    Dr. JC Gumbart, School of Physics, Georgia Institute of Technology (Advisor)

Dr. Jennifer Curtis, School of Physics, Georgia Institute of Technology

Dr. Daniel Goldman, School of Physics, Georgia Institute of Technology

Dr. David Sherrill, School of Chemistry and Biochemistry, Georgia Institute of Technology

Dr. Matthew Torres, School of Biological Sciences, Georgia Institute of Technology

Abstract:

Biomolecules, ranging from small molecules like vitamins to proteins, play critical roles in sustaining cellular functions. Their functionality is closely tied to their ability to undergo conformational changes in response to environmental conditions or binding events.  In drug design, understanding the conformational flexibility of small molecules is crucial. Small molecules can undergo conformational changes that affect their interactions with target proteins. This understanding is vital for predicting drug behavior and interactions in biological systems. Proteins, which are central to various biological processes, have intricate conformational dynamics. They can shift between various conformations to fulfill their functions, from subtle side chain rearrangements to extensive structural changes. Misfolded proteins can lead to diseases, making the study of protein conformational changes critical in both understanding biological processes and developing therapies. Molecular dynamics simulations offer a powerful tool for studying biomolecular dynamics. These simulations allow for precise control and measurement of various aspects of biomolecular systems, providing insights into their structural dynamics. However, some biological processes occur on long timescales, necessitating enhanced sampling techniques to accelerate simulations and capture rare events. In this thesis, we investigated three distinct biomolecular systems: capsid assembly modulator AT130, passenger domain of pertactin, and SARS-CoV-2 spike protein. Employing advanced simulation techniques and enhanced sampling methods, we delved into the intricate behaviors of these biomolecules, each representing a unique aspect of biological complexity. During this exploration, I also updated the open-source parameterization tool, Force Field Toolkit, to accommodate the novel sigma-hole particle (LP) introduced in CGenFF 4.0. Our research spanned a range of scales and complexities, showcasing the adaptability and relevance of simulations and enhanced sampling approaches in the study of diverse biological systems.