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Dissertation/Thesis Abstract

Investigating Butyrylcholinesterase Inhibition via Molecular Mechanics
by Alvarado, Walter, M.S., California State University, Long Beach, 2017, 90; 10639439
Abstract (Summary)

We show that a combination of different theoretical methods is a viable approach to calculate and explain the relative binding affinities of inhibitors of the human butyrylcholinesterase enzyme. We probe structural properties of the enzyme-inhibitor complex in the presence of dialkyl phenyl phosphates and derivatives that include changes to the aromatic group and alkane-to-cholinyl substitutions that help these inhibitors mimic physiological substrates. Monte Carlo docking allowed for the identification of three regions within the active site of the enzyme where substituents of the phosphate group could be structurally stabilized. Computational clustering was used to identify distinct binding modes and their relative stabilities. Molecular dynamics suggest an essential asparagine residue not previously characterized as strongly influencing inhibitor strength which may serve as a crucial component in catalytic and inhibitory activity. This study provides a framework for suggesting future inhibitors that we expect will be effective at sub-micromolar concentrations.

Indexing (document details)
Advisor: Bill, Andreas
Commitee: Gredig, Thomas, Sorin, Eric
School: California State University, Long Beach
Department: Physics and Astronomy
School Location: United States -- California
Source: MAI 57/01M(E), Masters Abstracts International
Subjects: Computational physics, Physics, Biophysics
Keywords: Biochemistry, Biophysics, Computational physics
Publication Number: 10639439
ISBN: 978-0-355-52948-7
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