Amyloid peptide Aβ40 inhibits aggregation of Aβ42: Evidence from molecular dynamics simulations

Effects of amyloid beta (A beta) peptide A beta(40) on secondary structures of A beta(42) are studied by all-atom simulations using the GROMOS96 43a1 force field with explicit water. It is shown that in the presence of A beta(40) the beta-content of monomer A beta(42) is reduced. Since the fibril-prone conformation N* of full-length A beta peptides has the shape of beta strand-loop-beta strand this result suggests that A beta(40) decreases the probability of observing N* of A beta(42) in monomer state. Based on this and the hypothesis that the higher is the population of N* the higher fibril formation rates, one can expect that, in agreement with the recent experiment, A beta(40) inhibit fibril formation of A beta(42). It is shown that the presence of A beta(40) makes the salt bridge D23-K28 and fragment 18-33 of A beta(42) more flexible providing additional support for this experimental fact. Our estimation of the binding free energy by the molecular mechanics-Poisson-Boltzmann surface area method reveals the inhibition mechanism that A beta(40) binds to A beta(42) modifying its morphology. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4730410]