Design of Protein Sequences which Fold into Secondary Structures using an Explicit Solvent Model

Abstract

The folding of proteins into helices and beta sheets has been investigated for the past five decades. To date, there has not been a thorough understanding of the physics behind this. Theoretical predictions by Zimm and Bragg give us some information but many studies have revealed contradicting results. For example short chain polyalanine, which according to Zimm and Bragg should form a random coil forms an unusually stable helix in solution and some peptides which have a low propensity for helix formation according to the theory tend to form stable helices. In the current work we seek the helix and beta sheet forming properties of individual short peptides using a simplistic model with explicit solvent through Monte Carlo simulations. The protein back bone and side chains are represented as either hard spheres (hydrophobic) or Jagla particles (hydrophilic) in a Jagla solvent. The helix and beta sheet forming tendencies are studied while varying the chain length, backbone sequence, size of the side group and the strength of the interactions.