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.
|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|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be