Project abstract for group sachsjn

Molecular Dynamics Studies of Membrane Proteins

These researchers are using MSI resources for three projects. The first is an investigation of αSynuclein (αS) membrane interactions. αS is the primary protein found in Lewy bodies that are the hallmark of Parkinson’s disease. This work uses a combination of X-ray and coarse-grained molecular dynamics (MD) simulations. The researchers explore how αS changes the structure and dynamics of the membrane, alterations that help explain the physical underpinnings of its action in fusion, fission and potentially disease.

The second project Investigates the tumor necrosis factor (TNF) superfamily of receptors, a class of membrane proteins that are targeted in cancer and inflammatory disease. The research uses a combination of cell/molecular biology and biophysical techniques in human cancer and model cells lines, along with synthetic biochemistry and computational modeling. The researchers use simulations to study the underlying structures that facilitate supra-molecular clustering of the receptors, in particular the transmembrane domains.

In the final project, the researchers study the cholesterol-recognition amino-acid consensus sequence (CRAC) motif because of its importance in dictating membrane protein trafficking. One example, the LWYIK peptide, binds within the lipid headgroup region and partitions into ordered regions of the membrane because of its direct interaction with cholesterol. The researchers are testing the hypothesis that this interaction stabilizes raft-like domains by both altering the line tension at the domain boundaries and relieving the strain on lipid headgroups that they have shown otherwise exists to shield cholesterol from water. 

A bibliography of this group’s publications acknowledging MSI is attached.