Exploring the Mechanosensitivity of membrane protein using steered molecular dynamics simulation
Poudel, Bharat
Poudel, Bharat
Citations
Altmetric:
License
License
Abstract
We used steered molecular dynamics simulations to explore the hydrophobic barrier within the two-pore domain potassium channel TWIK-1 and drive the AT1R from inactive to the active state as well. This hydrophobic barrier is formed by Leucine 146 and Leucine 261 that lie below the selectivity filter on the cytoplasmic side of the protein. Experimental studies have shown that mutations of Leucine 146 and 261 allow more water to permeate to the selectivity filter and increase ion conduction. We use a collective variable (CV) that mimics tension by applying forces on lipids in the vicinity of the channel based on their proximity to explore the role of membrane interactions in modulating the hydrophobic barrier. By applying a harmonic potential to this CV, we observed different solvent accessibility to the selectivity filter. Our results on AT1R show that pulling the protein with constant velocity will drive the system from inactive to active state. We applied less force (4 times) on the periplasmic side of the protein than the cytoplasmic side. we pulled continuously for 4 ns and see that the cytoplasmic side of Trans Membrane helix 6 ( TM6) shifted by an angle of 16 degree
Description
Date
2019-01-01
Student Status
Graduate
Journal Title
Journal ISSN
Volume Title
Type of presentation
Poster Presentation
Collections
Research Projects
Organizational Units
Journal Issue
Citation
DOI
Advisor(s)
Department
Program/Major
Materials Science
College/School
College of Engineering and Mathematical Sciences
Organization
item.page.researchcategory
Engineering & Physical Sciences
Biological Sciences
Biological Sciences