Folding and unfolding of chicken villin headpiece: energy landscape of a single-domain model protein

Abstract

Folding and unfolding of a thermostable chicken villin headpiece subdomain, a 36-residue protein (HP-36), is studied by using Brownian dynamics simulations. The hydropathy scale of amino acids is used to obtain the varying interactions among the amino acids. A qualitative picture of the energy landscape funnel is obtained from simulations. Although there are several states near the minimum of the folding funnel, we could identify a stable native configuration. The energy of the folded protein scales with the hydrophobic contact parameter, as found in recent analyses. The model also allows for a description of cold denaturation by the salt-induced modification of the 'effective' interactions among the various amino acids. In this model, the kinetics of denaturation is found to be considerably different from that of folding- folding, seems to face more barriers and involves a more complex pathway.