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                                           BIOINFORMATICS COLLOQUIUM
					       College of Science
                                            George Mason University
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				Membrane A-beta peptides(25-35 and 31-35) interaction 
					
					      	     Buyong Ma
					   National Cancer Institute, NIH

Abstract:
Amyloids might have common toxic mechanism. However, it is still controversial
about the relationship of amyloid deposition and cellular toxicity. One
critical mechanism of the cytotoxicity is that the amyloid proteins/peptides
form unregulated ion channels in membrane.  Ion channels formed by Alzheimer's
peptide implicated for Alzheimer's disease pathophysiology. However, the
molecular mechanism of the ion channel is still unknown. Here we test several
possibilities for Alzheimer's peptide fragments A-beta 31-35, A-beta25-35, and
A-beta 25-36 to ion channel.  Experimentally, A-beta 25-35 forms amyloid and is
neurotoxic;  A-beta 25-35 amide and A-beta 25-36 form amyloid without
neurotoxicity.  Molecular dynamics simulations with CHARMM27 force-field show
that while beta-sheet oligomers for all three variants are stable in solution,
not all of them form stable ion channel in membrane. Therefore, the ability to
form beta-amyloid can facilitate the ion channel formation, but not necessitate
the ion channel formation in membrane.