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.
| Identifer | oai:union.ndltd.org:MSSTATE/oai:scholarsjunction.msstate.edu:td-6998 |
| Date | 08 December 2023 |
| Creators | Beard, Torien M. |
| Publisher | Scholars Junction |
| Source Sets | Mississippi State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
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