Theses and Dissertations

Issuing Body

Mississippi State University

Advisor

Gwaltney, Steven R.

Committee Member

Emerson, Joseph E.

Committee Member

Webster, Charles E.

Date of Degree

12-8-2023

Original embargo terms

Embargo 1 Year

Document Type

Graduate Thesis - Open Access

Major

Chemistry

Degree Name

Master of Science (M.S.)

College

College of Arts and Sciences

Department

Department of Chemistry

Abstract

Computational methods such as Molecular Dynamics (MD) simulations and Molecular Mechanics generalized Born surface area solvation (MM-GBSA) binding affinity calculations have been utilized to determine the binding modes and final binding affinities of small molecules that are known to interact with the heart sodium channel NaV1.5. Lidocaine, ranolazine, and flecainide are FDA approved arrhythmia drugs that are prescribed to patients in the event of heart disease. Here, we demonstrate the likely binding preferences and modes of action of all molecules with NaV1.5, the stability of the systems, and overall final binding affinities of the small molecules with the protein. To gain insights into the mechanisms of heart disease treatments, the MM-GBSA method was utilized to estimate the binding free energies of each molecule and pose to NaV1.5. The evaluation of the binding of small molecules to NaV1.5 contributes to enhancing our understanding of the underlying processes involved in heart disease treatments. The MM-GBSA approach provides a valuable tool for predicting and analyzing binding affinities, which can aid in the design and optimization of potential therapeutic compounds targeting NaV1.5.

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