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Rational, Reproducible, and Rigorous Computational Enzymology: The Case of Catechol-O-Methyltransferase

preprint
submitted on 04.08.2020 and posted on 07.08.2020 by Thomas Summers, Qianyi Cheng, Manuel Palma, Diem-Trang Pham, Dudley Kelso III, Charles Edwin Webster, Nathan DeYonker
The efficiency, accuracy, and replicability of enzyme simulations is often hampered by ad hoc model design. To address this problem, we have developed the Residue Interaction Network ResidUe Selector (RINRUS) toolkit. RINRUS utilizes residue contact networks to automate construction of rational quantum mechanical cluster models. This work examines this problem by computing the reaction kinetics and thermodynamics for 508 models of the active site of catechol-o-methyltransferase, an enzyme which catalyzes the methyl transfer from S-adenosyl methionine cofactor to catechol substrates. Our results demonstrate using RINRUS to rationally design small and accurate active site models.

Funding

Graduate Research Fellowship Porgram (GRFP)

Directorate for Education & Human Resources

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CAREER: Innovation: The Three R's: A Model-Building Toolkit for Rational, Reproducible, and Rigorous Computational Enzymology

Directorate for Biological Sciences

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CAREER: Mind your P's and O's--Theoretical Studies on Phosphoryl Transfer Enzymes: Transition-State Analogues and Catalysis

Directorate for Mathematical & Physical Sciences

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CAREER: Mind your P's and O's--Theoretical Studies on Phosphoryl Transfer Enzymes: Transition-State Analogues and Catalysis

Directorate for Mathematical & Physical Sciences

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History

Email Address of Submitting Author

tsmmers1@memphis.edu

Institution

University of Memphis

Country

United States of America

ORCID For Submitting Author

0000-0002-4243-6078

Declaration of Conflict of Interest

The authors declare that there is no conflict of interest.

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