Molecular Dynamics Simulations of the Folding of Chameleon Sequences

Protein folding refers to the process by which proteins reach their biologically active state. Both sequence and context influence the folding process to a given three-dimensional fold. Chameleon sequences are short sequences (usually less than 8 amino acids long) that adopt helical or sheet structure, depending on their environment. Using replica exchange molecular dynamics simulations, we have investigated the folding of the FALDLLME and KLSESQL Chameleon sequences in three different environments: 1) in isolation; 2) with helical flanking residues and 3) with sheet flanking residues. Our simulations reveal that the peptide, in isolation, does not possess any intrinsic propensity to populate either a helical or sheet conformation. The addition of flanking residues, however, leads to population of either helical or sheet structure. We are designing new, minimalist flanking regions with the goal of controlling the mechanistic switch from helical to sheet and vice-versa.