Forcefield evaluation and accelerated molecular dynamics simulation of Zn(II) binding to N-terminus of amyloid-β

Accelerated molecular dynamics is used to explore the binding of Zn N-terminal fragment amyloid-β, and test performance AMBER-style forcefields. • AMBER forcefield reproduces NMR structure Zn(II) bound Aβ. Implicit solvent performs at least as well explicit in this regard. MD shows subtle difference for different modes. Free energy surface restriction size flexibility due Zn-binding. We report conventional accelerated simulation N-terminus amyloid-β. By comparison against data experimentally determined mode, we find that certain combinations model perform acceptably describing size, shape secondary structure, there no appreciable between implicit models. therefore combination ff14SB GBSA compare result modes same peptide, using enhance sampling comparing free peptide simulated way. show imparts significant rigidity disrupts pattern salt bridges seen induces closer contact residues. surfaces 1 or 2 dimensions further highlight effect metal coordination on peptide’s spatial extent. also provide evidence provides improved over by visiting many more configurations much shorter times.