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Department or Program Affiliation
Master of Science (MS)
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.
Molecular Dynamics, QM/MM, Enhanced Sampling Methods, Metadynamics, Computational Biochemistry, Enzyme
Western Washington University
Subject – LCSH
Molecular dynamics--Study and teaching; Biochemistry--Research; Sampling
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Enciso, Edwin, "Exploring Biochemical Mechanisms with Hybrid Quantum Mechanics/Molecular Mechanics and Enhanced Sampling Methods" (2021). WWU Graduate School Collection. 1048.