Primary Faculty Mentor Name

Juan Vanegas

Project Collaborators

Rajitha Tatikonda (Collaborating Mentor), Juan Vanegas (Graduate Student Mentor)

Graduate Student Mentors

Juan Vanegas

Status

Graduate

Student College

College of Engineering and Mathematical Sciences

Program/Major

Materials Science

Primary Research Category

Engineering & Physical Sciences

Secondary Research Category

Biological Sciences

Presentation Title

Exploring the Mechanosensitivity of membrane protein using steered molecular dynamics simulation

Time

3:00 PM

Location

Silver Maple Ballroom - Engineering & Physical Sciences

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

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Exploring the Mechanosensitivity of membrane protein using steered molecular dynamics simulation

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