biostudies-literatureReddy GNIGMS NIH HHS1162-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC3098509biostudies-literatureUnknown113(4)Recent experiments have shown that the congener Abeta(1-40)[D23-K28], in which the side chains of charged residues Asp23 and Lys28 are linked by a lactam bridge, forms amyloid fibrils that are structurally similar to the wild type (WT) Abeta peptide, but at a rate that is nearly 1000 times faster. We used all atom molecular dynamics simulations in explicit water, and two force fields, of the WT dimer, a monomer with the lactam bridge (Abeta(10-35)-lactam[D23-K28]), and the monomer and dimers with harmonically constrained D23-K28 salt bridge (Abeta(10-35)[D23-K28]) to understand the origin of the enhanced fibril rate formation. The simulations show that the assembly competent fibril-like monomer (N*) structure, which is present among the conformations sampled by the isolated monomer, with sThe journal of physical chemistry. BInfluence of preformed Asp23-Lys28 salt bridge on the conformational fluctuations of monomers and dimers of Abeta peptides with implications for rates of fibril formation.PMC3098509R01GM076688-05R01 GM076688R01 GM076688-08Reddy GStraub JEThirumalai DfalseInfluence of preformed Asp23-Lys28 salt bridge on the conformational fluctuations of monomers and dimers of Abeta peptides with implications for rates of fibril formation.Recent experiments have shown that the congener Abeta(1-40)[D23-K28], in which the side chains of charged residues Asp23 and Lys28 are linked by a lactam bridge, forms amyloid fibrils that are structurally similar to the wild type (WT) Abeta peptide, but at a rate that is nearly 1000 times faster. We used all atom molecular dynamics simulations in explicit water, and two force fields, of the WT dimer, a monomer with the lactam bridge (Abeta(10-35)-lactam[D23-K28]), and the monomer and dimers with harmonically constrained D23-K28 salt bridge (Abeta(10-35)[D23-K28]) to understand the origin of the enhanced fibril rate formation. The simulations show that the assembly competent fibril-like monomer (N*) structure, which is present among the conformations sampled by the isolated monomer, with s2009-01-01T00:00:00Z2009 Jan2025-04-19T16:29:46.682Z2019-03-27T00:41:48ZS-EPMC30985091912557410.1021/jp808914c