Kinetic Modeling of the Ensemble of Pathways Present in Conformational Dynamics
Open Access
Author:
Wolfe, David K
Graduate Program:
Chemistry
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
April 26, 2019
Committee Members:
Edward Patrick O'Brien, Jr., Thesis Advisor/Co-Advisor Lasse Jensen, Committee Member William George Noid, Committee Member
Keywords:
Chemical Physics Markov State Models Chain-of-States First Passage Time Kramers Theory
Abstract:
Chemical reactions in biology occur in high dimensional space and at physiological temperatures, thereby ensuring that there are multiple reaction pathways connecting an ensemble of reactant and an ensemble of product states. Current methods in the computational chemistry field attempt to describe such a reaction using a single reaction pathway at zero Kelvin, or as an ensemble of pathways restricted locally to be near the minimum energy path. Here, we develop a new computational method that allows us to describe multiple pathways by using a novel combination of Markov state modeling and chain-of-states methods. The method is verified first on an analytical surface, followed by application to several dipeptide molecules. We find that our method is able to accurately predict the kinetics of the system and we show that the consideration of multiple pathways more accurately describes the trend in overall rate at a series of temperatures and the overall observed flux.
