Date of Award

2022

Document Type

Honors Thesis (Open Access)

Department

Colby College. Chemistry Dept.

Advisor(s)

Dr. Lindsey R. Madison

Second Advisor

Dr. Dasan M. Thamattoor

Abstract

Voltage gated sodium ion channels are implicated in cardiac diseases, seizures, etc., and they play a role in maintaining ionic homeostasis in cells. Computational studies use prokaryotic model because they are simpler but function similarly to human voltage gated sodium ion channels. This study uses molecular dynamics (MD) to study three specific questions regarding voltage gated sodium ion channels of Magnetococcus marinus. The first question in this study is how the free energy of sodium diffusion compares to that of calcium ion diffusion. We were not able to find any physically significant information due to poor sampling and a lack of ion diffusion. We also examined the role of the hydration shell and protonation state in conferring selectivity to the voltage gated sodium ion channel. This study does not find evidence that the size of the hydration shell or protonation state of the glutamate ring in the selectivity filter contributes to selectivity against calcium ions. Additionally, the water itself has no significant interactions with the amino acid residues. A key conclusion from this study is that approximating the location of the uncrystallized residues using the GalaxyFill algorithm does not accurately represent experimental voltage gated ion channels because it occasionally predicts non-physical conformations that result in the interlocking of rings of the residues with other residues and may be biased towards the formation of loops in the system.

Keywords

Molecular Dynamics, NAMD, Voltage-gated sodium ion channels

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