Investigations on the alpha-helix to coil transition in HP heterogeneous polypeptides usingnetwork rigidity

Abstract

The alpha-helix to coil transition in homogeneous polypeptides has recently been describedusing a distance constraint model (DCM) that employs network rigidity as an underlyingmechanical interaction. The DCM accounts for intramolecular hydrogen bonding, hydrogenbonding to solvent and hydration. These interactions are parametrized to reflect thedependence on the conformational state of the polypeptide backbone. The DCM is capableof describing both heat and cold denaturation. As a function of temperature from low tohigh, a generic re-entrant response of a homogeneous polypeptide chain in aqueous solutionis predicted to make a transition from coil (hydrated state) to helix and then to coil(disordered state). Here we study the thermodynamic stability of heterogeneouspolypeptides that include hydrophobic (H) and polar (P) residue types. We explore thenature of the transition by adjusting the overall HP composition using transfermatrix methods that take into account long-range effects due to network rigidity.