1. Interaction of A28-35 with POPG lipid bilayer
Zhongwen Chang, Guanghong Wei
Department of Physics, Fudan University, Shanghai , China
Abstract: Amyloid beta (A) is a peptide of 39–43 amino acids that appear to be the main constituent of amyloid plaques in the brains of Alzheimer's disease patients. We study the conformational dynamics of the fragment of (A28-35) from the full-length A in the presence of POPG lipid bilayer and try to find out the interaction core as well as the effect of peptide-lipid interaction on the lipid bilayer.
Motivation: The interaction of A peptide with neuronal membranes could play a key role in the pathogenesis of Alzheimer’s disease. S Nagarajan et. al. has investigated the interaction of lipid with soluble A and found that, upon addition of negatively charged PG lipids the protein fragment reorganized into a predominant beta-sheet structure while zwitterionic PC lipids had no effect on the conformational change. However, the entire conformational transition process is yet fully understood.
Method: molecular dynamics simulation with GROMOS force field in GROMACS software. Parameters are varied according to different conditions.
Preliminary results:
Simulation time: 50 ns,T=315 K, PH≈7
Initial structure, distance between proteins is 4.84 Å.
First parallel beta appears in IIGL segment at t=15 ps (lipid not shown).
beta-sheet stays at t=1 ns.
DSSP plot shows the time evolution of the secondary structure of each amino acid.
t= 50 ns, bilayer has distorted.
Expectation: The secondary structure of A28-35 on POPG lipid bilayer is expected to varies from random coil to a beta sheet structure in the existence of POPG bilayer. Further studies are needed to show how the POPG bilayer effects the secondary structure of the peptide, and what exact interaction play the main role .
References:
1. Elmore, D. E. FEBS Lett. 2006, 580: S. Nagarajan et al. FEBS J., 2008, 275: 2415.