Computational methods for structural and functional studies of alzheimer’s amyloid ion channels

Abstract

Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, acrosssolid surfaces, and on and in the membrane, where they may assemble into unregulated leaking ion channels. Experimental probes of ion channel conformations and dynamics are challenging. Atomistic molecular dynamics (MD) simulations are capable of providing insight intostructural details of amyloid ion channels in the membrane at aresolution not achievable experimentally. Since data suggest that late stage Alzheimer’s disease involves formation of toxic ion channels, MD simulations have been used aiming to gain insight into the channel shapes, morphologies, pore dimensions, conformational heterogeneity, and activity. These can beexploited for drug discovery. Here we describe computational methods to model amyloid ion channels containing the β-sheet motif at atomic scale and to calculate toxic poreactivity in the membrane.