(588d) Molecular Dynamics Simulations of Peptide Self-Assembly Under Confinement

Molecular dynamics simulations of self-assembled peptide aggregates have commonly been investigated under bulk conditions, however to more accurately represent the crowded, heterogeneous environment of a cell, it is necessary to perform studies of protein folding and aggregation under confinement. In this work, we look at three peptide sequences (KA14K, WQVQVEVQVEVQVQVQV, & WQVEVQVQVQVQVEVQV), to study their individual aggregation processes starting from a random configuration when confined between two surfaces. In general, we investigate how confinement influences the kinetics of aggregation compared to bulk. Since long-range interactions especially those between charged groups are most affected by confinement, we examine how the location of charged amino acid residues modify the kinetics and final self-assembled structures. To achieve this we use an extended version of a coarse-gained amino acid model, PRIME (Protein Intermediate Resolution Model), and utilize Discontinuous Molecular Dynamics in order to obtain the long time scales needed to study aggregation. Our results indicate that confinement increases the propensity to form beta-structures. Moreover, the position of the charged residues determines the location and length of a beta-strand. In addition, we propose general guidelines for how the placement of electrostatic residues in a peptide affects the assembly of ordered structures.