First Advisor
Steve L. Reichow
Date of Award
6-16-2021
Document Type
Thesis
Degree Name
Bachelor of Science (B.S.) in Computer Science and University Honors
Department
Computer Science
Language
English
Subjects
Connexins, Gap junctions (Cell biology), Molecular dynamics
DOI
10.15760/honors.1062
Abstract
Connexins form intercellular channels known as gap junctions that facilitate diverse physiological roles, from long-range electrical and chemical coupling to nutrient exchange. Recent structural studies on Cx46 and Cx50 have defined a novel and stable open state and implicated the amino-terminal (NT) domain as a major contributor to functional differences between connexin isoforms. This thesis presents two studies which use molecular dynamics simulations with these new structures to provide mechanistic insight into the function and behavior of the NTH in Cx46 and Cx50. In the first, residues in the NTH that differ between Cx46 and Cx50 are swapped between the two isoforms to identify the particular positions that form the key structural and energetic barriers of ion permeation. In the second, a known cataract-associated mutation is modeled and simulated in Cx50, demonstrating potential atomic interactions with the NTH that could lead to the observed disease phenotype. Together, these studies deepen the field's knowledge of the role of the connexin NT domain, with novel atomic-level detail, and demonstrate how simulation can be combined with experimental methods to better understand the interplay between gap junction structure and function.
Rights
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Persistent Identifier
https://archives.pdx.edu/ds/psu/35678
Recommended Citation
Khan, Umair, "Functional Role of the N-terminal Domain in Connexin 46/50 by in silico Mutagenesis and Molecular Dynamics Simulation" (2021). University Honors Theses. Paper 1036.
https://doi.org/10.15760/honors.1062
Comments
An undergraduate honors thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in University Honors and Computer Science & Mathematics.