Simulation of Helix Formation and Analysis by Lifson-Roig Theory

The predilection for short polypeptides to adopt different secondary structural elements, like α-helicies, is encoded in their amino acid sequences. Lifson-Roig is a helix-coil transition theory that predicts the melting curves based on their specific sequences from parameters fitted to fractional helicities determined from circular dichroism experiments. Lifson-Roig theory makes predictions regarding the distribution of helix probabilities along the peptide backbone that is experimentally unavailable. We have performed replica exchange molecular dynamic simulations (REMD) to evaluate helix formation for a large set of polypeptide chains at temperatures ranging from ~250 K to ~350 K. Accurate helical nucleation and propagation probabilities down the simulated peptide sequences were determined. While Lifson-Roig theory accurately reproduces the fractional helicities from simulation, the comparison between the predicted and observed backbone distribution of helical amino acids is only qualitative. These results suggest a moderately longer-range interaction between amino acids in the stabilization of helical structures than assumed by Lifson-Roig.