Using molecular dynamics to probe protein conformational transition mechanisms at the membrane surface
type: CreativeWork
description: Far from being a passive demarcation between the cell and the environment, the cellular membrane is a vibrant and dynamic ecosystem. Membrane proteins constitute an integral piece of this ecosystem, allowing for communication between the cell and its environment that is necessary for adaptation and robustness of the cell. Often, membrane proteins are expressed in a default inactive state requiring a signal from either the extracellular milieu or from the cell itself to be activated, undergoing a significant structural shift in order to perform its function. Due to the transient nature of these activated states, however, it has been difficult to characterize the structural transitions needed to activate peripheral and integral membrane proteins. The work presented herein leverages molecular dynamics (MD) simulations as a method to explore and characterize the dynamics of both peripheral and integral membrane proteins in the context of the membrane. While MD simulations have unrivaled spatiotemporal resolution, the timescales accessible to MD simulations often prevents characterization of spontaneous membrane insertion of peripheral proteins. Many biasing protocols have been developed to observe the binding of peripheral membrane proteins on the timescales routinely accessible in MD simulations. These protocols, however, inherently bias the final structure derived from the study. A novel membrane mimetic model, termed the highly mobile membrane mimetic (HMMM), is presented which shows expedited lipid dynamics and decreased time to insertion for peripheral proteins. The physicochemical properties of the model are fully characterized and compared to conventional membranes, showing good agreement with key elastic, electric, and energetic properties of the membrane. Moreover, the HMMM model is utilized to simulate the unbiased binding of a peripheral protein, the talin F2F3 subdomain. In addition to characterizing the membrane-bound form of this protein, which has remaine…
abstract: Far from being a passive demarcation between the cell and the environment, the cellular membrane is a vibrant and dynamic ecosystem. Membrane proteins constitute an integral piece of this ecosystem, allowing for communication between the cell and its environment that is necessary for adaptation and robustness of the cell. Often, membrane proteins are expressed in a default inactive state requiring a signal from either the extracellular milieu or from the cell itself to be activated, undergoing a significant structural shift in order to perform its function. Due to the transient nature of these activated states, however, it has been difficult to characterize the structural transitions needed to activate peripheral and integral membrane proteins. The work presented herein leverages molecular dynamics (MD) simulations as a method to explore and characterize the dynamics of both peripheral and integral membrane proteins in the context of the membrane. While MD simulations have unrivaled spatiotemporal resolution, the timescales accessible to MD simulations often prevents characterization of spontaneous membrane insertion of peripheral proteins. Many biasing protocols have been developed to observe the binding of peripheral membrane proteins on the timescales routinely accessible in MD simulations. These protocols, however, inherently bias the final structure derived from the study. A novel membrane mimetic model, termed the highly mobile membrane mimetic (HMMM), is presented which shows expedited lipid dynamics and decreased time to insertion for peripheral proteins. The physicochemical properties of the model are fully characterized and compared to conventional membranes, showing good agreement with key elastic, electric, and energetic properties of the membrane. Moreover, the HMMM model is utilized to simulate the unbiased binding of a peripheral protein, the talin F2F3 subdomain. In addition to characterizing the membrane-bound form of this protein, which has remaine…
author: Arcario, Mark
language: en
keywords: Molecular Dynamics, Membrane Protein, Coagulation, Talin, Integrin, Anesthetics, Gloeobacter violaceus ligand-gated ion channel (GLIC), Ion Channel
date published: 2015-01-21T19:48:03Z
date modified: 2026-07-22T22:26:07Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/72776