tailieunhanh - Báo cáo khoa học: Perturbation of membranes by the amyloid b-peptide – a molecular dynamics study

The etiology of Alzheimer’s disease is considered to be linked to interac-tions between amyloid b-peptide (Ab) and neural cell membranes. Mem-brane disruption and increased ion conductance have been observed in vitro in the presence of Ab, and it is assumed that these same phenom-ena occur in the brain of an individual afflicted with Alzheimer’s. | Perturbation of membranes by the amyloid b-peptide -a molecular dynamics study Justin A. Lemkul and David R. Bevan Department of Biochemistry Virginia Polytechnic Institute and State University Blacksburg VA USA Keywords Alzheimer s amyloid membrane protein-lipid interactions simulation Correspondence D. R. Bevan Department of Biochemistry Virginia Polytechnic Institute and State University 201 Fralin Biotechnology Center Blacksburg VA 24061 USA Fax 1 54o 231 9070 Tel 1 540 231 5040 E-mail drbevan@ Website http Received 19 February 2009 revised 24 March 2009 accepted 26 March 2009 doi The etiology of Alzheimer s disease is considered to be linked to interactions between amyloid b-peptide Ab and neural cell membranes. Membrane disruption and increased ion conductance have been observed in vitro in the presence of AP and it is assumed that these same phenomena occur in the brain of an individual afflicted with Alzheimer s. The effects of AP on lipid behavior have been characterized experimentally but details are lacking regarding how AP induces these effects. Simulations of AP in a bilayer environment can provide the resolution necessary to explain how the peptide interacts with the surrounding lipids. In the present study we present an extensive analysis of lipid parameters for a model dipalmitoylphosphatidylcholine bilayer in the presence of the 40-residue Ab peptide AP40 . The simulated systems examine the effects of the insertion depth of the peptide temperature the protonation state of the peptide and ionic strength on the features of the lipid bilayer. The results show that Ab40 is capable of disordering nearby lipids as well as decreasing bilayer thickness and area per lipid headgroup. These phenomena arise as a result of the unfolding process of the peptide which leads to a disordered extended conformation that is capable of extensive electrostatic and hydrogen-bonding interactions between the