Nonequilibrium molecular dynamics simulations of infrared laser-induced dissociation of a tetrameric Aβ42 β-barrel in a neuronal membrane model

Experimental studies have reported that the amyloid-β proteins can form pores in cell membranes, and this could be one possible source of toxicity Alzheimer's disease. Dissociation these therefore a potential therapeutic approach. It is known high photon density free-electron laser experiments laser-induced nonequilibrium molecular dynamics simulations (NEMD) dissociate amyloid fibrils at specific frequencies vitro. Our question whether NEMD bilayer mimicking neuronal membrane, as an example, we select tetrameric Aβ42 β-barrel. shows resonance between field amide I vibrational mode barrel destabilises all intramolecular intermolecular hydrogen bonds converts β-barrel to random/coil disordered oligomer. Starting from oligomer, extensive standard MD sampling states without any increase β-sheet reports orientational order lipids minimally disturbed. Interestingly, frequency employed beta-barrel amino acid sequence. Taken together with our previous simulation results, study indicates infrared irradiation oligomers bulk solution membrane environment affecting surrounding molecules, offering promising way retard progression AD.