Monte Carlo Simulations of the Effect of a Turn Sequence in an Alanine-Based Peptide

Abstract

Alanine-based peptides are known to form single alpha helical chains. Furthermore, PSDP sequences form turns in the two-helix bundle needle proteins from type III secretion systems. To determine if the PSDP sequence would bias an alanine-based peptide toward a two helix bundle, we have carried out Monte Carlo simulations of an alanine-based peptide with and without a PSDP sequence in the middle of the peptide. Because needle proteins are 40 to 45 residues in length, we used 42 residue peptides in our simulations. The alanine-based peptide consisted of a (AAAAAK)7 sequence which we call AK42, whereas the AK42_PSDP peptide inserted a PSDP sequence centrally by replacing the fourth repeat of (AAAAAK)7 with APSDPK. We carried out Replica Exchange Monte Carlo simulations on the two peptides using the CAMPARI simulation package. A total of 16 temperatures ranging from 280 K to 460 K were used to monitor the globule to coil transition for our two peptide models. Our data show a stabilization of the globule form of AK42_PSDP to higher temperatures when monitoring the radius of gyration (Rg) compared to that of AK42. We will also report on the position of chain reversals using clustering algorithms which allow us to see prominent structures at each temperature and thus the influence of the PSDP sequence on the narrowness of the conformational distribution of the alanine-based peptide.