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A molecular dynamics study of the early stages of amyloid‐β(1–42) oligomerization: The role of lipid membranes
Author(s) -
Davis Charles H.,
Berkowitz Max L.
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22763
Subject(s) - chemistry , dipalmitoylphosphatidylcholine , dimer , bilayer , membrane , lipid bilayer , biophysics , peptide , molecular dynamics , phospholipid , biochemistry , computational chemistry , organic chemistry , phosphatidylcholine , biology
As research progresses toward understanding the role of the amyloid‐β (Aβ) peptide in Alzheimer's disease, certain aspects of the aggregation process for Aβ are still not clear. In particular, the accepted constitution of toxic aggregates in neurons has shifted toward small oligomers. However, the process of forming these oligomers in cells is also not full clear. Even more interestingly, it has been implied that cell membranes, and, in particular, anionic lipids within those membranes, play a key role in the progression of Aβ aggregation, but the exact nature of the Aβ‐membrane interaction in this process is unknown. In this work, we use a thermodynamic cycle and umbrella sampling molecular dynamics to investigate dimerization of the 42‐residue Aβ peptide on model zwitterionic dipalmitoylphosphatidylcholine (DPPC) or model anionic dioleoylphosphatidylserine (DOPS) bilayer surfaces. We determined that Aβ dimerization was strongly favored through interactions with the DOPS bilayer. Further, our calculations showed that the DOPS bilayer promoted strong protein–protein interactions within the Aβ dimer, whereas DPPC favored strong protein–lipid interactions. By promoting dimer formation and subsequent dimer release into the solvent, the DOPS bilayer acts as a catalyst in Aβ aggregation. Proteins 2010. © 2010 Wiley‐Liss, Inc.