Molecular modelling of peptide folding, misfolding and aggregation phenomena

In this article we present computer modelling studies using classical molecular dynamics techniques and their derivative methods such as umbrella sampling and bias-exchange metadynamics to investigate protein folding, misfolding and aggregation behaviour under various conditions. The effects of oxidation, mutation and lipid concentrations on the structure and dynamics of a peptide model were investigated in detail. The relative stability of pre-formed fibrils and the effect of termini charge were studied to elucidate the initial stages of fibril formation. Using computational techniques we were able to identify key conformational features and kinetic mechanisms relevant to the fibrillation propensities of the peptide models. Here we present applications related to two important proteins–insulin and apolipoprotein C-II (ApoC-II)