Impact of Turn Propensity on the Folding Rates of Z34C Protein: Implications for the Folding of Helix-Turn-Helix Motif.

The rate-limiting step for the folding of the helix-turn-helix (HTH) protein, Z34C, involves β-turn region DPNL. This reverse turn has been observed to be part of the transition state in the folding process for Z34C, influencing its folding rates. Molecular dynamics simulations were performed on this turn peptide and its two mutants, D20A and P21A, to study turn formation using GROMOS54A7 force field. We find that this region has a turn propensity of its own, and the highest turn propensity is observed for the wild-type, which correlates well with available experimental results. We also find that a slight unfavorable change in ΔG causes a drastic change in the folding rates of HTH motif and a mechanistic interpretation is given. Implications of these observations for the folding of the HTH protein Z34C are discussed.