The Structure of the Alzheimer Amyloid [beta] 10-35 Peptide Probed through Replica-Exchange Molecular Dynamics Simulations in Explicit Solvent

@article{citeulike:1281588, abstract = {The conformational states sampled by the Alzheimer amyloid [beta] (10-35) (A[beta] 10-35) peptide were probed using replica-exchange molecular dynamics (REMD) simulations in explicit solvent. The A[beta] 10-35 peptide is a fragment of the full-length A[beta] 40/42 peptide that possesses many of the amyloidogenic properties of its full-length counterpart. Under physiological temperature and pressure, our simulations reveal that the A[beta] 10-35 peptide does not possess a single unique folded state. Rather, this peptide exists as a mixture of collapsed globular states that remain in rapid dynamic equilibrium with each other. This conformational ensemble is dominated by random coil and bend structures with insignificant presence of an [alpha]-helical or [beta]-sheet structure. The 3D structure of A[beta] 10-35 is seen to be defined by a salt bridge formed between the side-chains of K28 and D23. This salt bridge is also observed in A[beta] fibrils and our simulations suggest that monomeric conformations of A[beta] 10-35 contain pre-folded structural motifs that promote rapid aggregation of this peptide.}, author = {Baumketner, Andrij and Shea, Joan-Emma }, citeulike-article-id = {1281588}, doi = {10.1016/j.jmb.2006.11.015}, journal = {Journal of Molecular Biology}, keywords = {replica-exchange, simulations}, month = {February}, number = {1}, pages = {275--285}, posted-at = {2008-01-21 18:24:06}, priority = {2}, title = {The Structure of the Alzheimer Amyloid [beta] 10-35 Peptide Probed through Replica-Exchange Molecular Dynamics Simulations in Explicit Solvent}, url = {http://dx.doi.org/10.1016/j.jmb.2006.11.015}, volume = {366}, year = {2007} }

TY - JOUR ID - citeulike:1281588 L3 - citeulike-article-id:1281588 TI - The Structure of the Alzheimer Amyloid [beta] 10-35 Peptide Probed through Replica-Exchange Molecular Dynamics Simulations in Explicit Solvent JF - Journal of Molecular Biology VL - 366 IS - 1 SP - 275 EP - 285 N2 - The conformational states sampled by the Alzheimer amyloid [beta] (10-35) (A[beta] 10-35) peptide were probed using replica-exchange molecular dynamics (REMD) simulations in explicit solvent. The A[beta] 10-35 peptide is a fragment of the full-length A[beta] 40/42 peptide that possesses many of the amyloidogenic properties of its full-length counterpart. Under physiological temperature and pressure, our simulations reveal that the A[beta] 10-35 peptide does not possess a single unique folded state. Rather, this peptide exists as a mixture of collapsed globular states that remain in rapid dynamic equilibrium with each other. This conformational ensemble is dominated by random coil and bend structures with insignificant presence of an [alpha]-helical or [beta]-sheet structure. The 3D structure of A[beta] 10-35 is seen to be defined by a salt bridge formed between the side-chains of K28 and D23. This salt bridge is also observed in A[beta] fibrils and our simulations suggest that monomeric conformations of A[beta] 10-35 contain pre-folded structural motifs that promote rapid aggregation of this peptide. KW - replica-exchange KW - simulations AU - Baumketner, Andrij AU - Shea, Joan-Emma PY - 2007/02/09/ UR - http://dx.doi.org/10.1016/j.jmb.2006.11.015 ER -