Recent experiments have shown that the congener Aβ1−40[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) Aβ 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 (Aβ10−35-lactam[D23−K28]), and the monomer and dimers with harmonically constrained D23−K28 salt bridge (Aβ10−35[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 strand conformations in the residues spanning the N and C termini and a bend involving residues D23VGSNKG29, are populated to a much greater extent in Aβ10−35[D23−K28] and Aβ10−35-lactam[D23−K28] than in the WT, which has negligible probability of forming N*. The salt bridge in N* of Aβ10−35[D23−K28], whose topology is similar to that found in the fibril, is hydrated. The reduction in the free energy barrier to fibril formation in Aβ10−35[D23−K28] and in Aβ10−35-lactam[D23−K28], compared to the WT, arises largely due to entropic restriction which enables the bend formation. A decrease in the entropy of the unfolded state and the lesser penalty for conformational rearrangement including the formation of the salt bridge in Aβ peptides with D23−K28 constraint results in a reduction in the kinetic barrier in the Aβ1−40-lactam[D23−K28] congener compared to the WT. The decrease in the barrier, which is related to the free energy cost of forming a bend, is estimated to be in the range (4−7)kBT. Although a number of factors determine the growth of fibrils, the decrease in the free energy barrier, relative to the WT, to N* formation is a major factor in the rate enhancement in the fibril formation of Aβ1−40[D23−K28] congener. Qualitatively similar results were obtained using simulations of Aβ9−40peptides and various constructs related to the Aβ10−35systems that were probed using OPLS and CHARMM force fields. We hypothesize that mutations or other constraints that preferentially enhance the population of the N* species would speed up aggregation rates. Conversely, ligands that lock it in the fibril-like N* structure would prevent amyloid formation. [ABSTRACT FROM AUTHOR]