The vast majority of theses in this collection are open access and freely available. There are a small number of theses that have access restricted to the WWU campus. For off-campus access to a thesis labeled "Campus Only Access," please log in here with your WWU universal ID, or talk to your librarian about requesting the restricted thesis through interlibrary loan.

Date Permissions Signed

7-16-2021

Date of Award

Summer 2021

Document Type

Masters Thesis

Department or Program Affiliation

Chemistry

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

McCarty, Jay

Second Advisor

Amacher, Jeanine

Third Advisor

Kowalczyk, Tim

Abstract

In the field of molecular dynamics (MD), a long-standing issue is the time frame required in order to fully observe a chemical reaction. Enhanced sampling methods have been the primary way of overcoming this issue for the past 40 years. In this experiment our goal was to combine new and existing sampling methods in order to create an efficient and accurate way of retrieving kinetics data from simulations. In order to do this, we examined two test cases: the enzymes chorismate mutase and cytosine deaminase. We did this using hybrid quantum mechanics/molecular mechanics simulations coupled with enhanced sampling methods. The electronic structure of the quantum region is computed at the semiempirical level. We used metadynamics enhanced sampling method to study the reaction within the enzyme active site by biasing along the reaction coordinate. This allowed us to estimate the barrier heights and transition state coordinates. We also used the variationally enhanced sampling method to probe reaction kinetics. This latter approach suffered from convergence issues leading us to consider more advanced collective variables or improvements to how the bias is optimized.

Type

Text

Keywords

Molecular Dynamics, QM/MM, Enhanced Sampling Methods, Metadynamics, Computational Biochemistry, Enzyme

Publisher

Western Washington University

OCLC Number

1264431336

Subject – LCSH

Molecular dynamics--Study and teaching; Biochemistry--Research; Sampling

Format

application/pdf

Genre/Form

masters theses

Language

English

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

Download

Included in

Chemistry Commons

Share

COinS