Dissertation/Thesis Abstract

Identification and Characterization of Protein-Ligand Binding Modes via Molecular Dynamics
by Bremer, Parker Ladd, M.S., California State University, Long Beach, 2019, 81; 13859447
Abstract (Summary)

One technique that rational drug design incorporates is molecular docking of a drug and a protein. This computationally fast approach provides insight into favorable amino acid-drug interactions that future drug designs can exploit. However, clustering of molecular dynamics can provide a more accurate and more complete picture of protein-drug interactions. While the computational demand of molecular dynamics made it previously inaccessible, advances in hardware and sampling approaches now allow this approach to be tractable. Therefore, we proposed, refined, and continue to develop a method to ascertain and describe a complete picture of drug and binding pocket interactions. This method was applied to butyrylcholinesterase in complex with alkyl aryl phosphates to explain the governing binding interactions as well as assayed binding affinity coefficients. Insights include steric explanations for choline behavior, the identification of the acyl binding site and glycine residues as important stabilizers, and the observation of two distinct binding motifs.

Indexing (document details)
Advisor: Sorin, Eric J.
Commitee: Mezyk, Stephen, Schwans, Jason
School: California State University, Long Beach
Department: Chemistry and Biochemistry
School Location: United States -- California
Source: MAI 81/1(E), Masters Abstracts International
Subjects: Computational chemistry, Biophysics
Keywords: Butyrylcholinesterase, Clustering, Descriptor, K-means, Molecular dynamics
Publication Number: 13859447
ISBN: 9781085557801
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