Study of pair contact formation among hydrophobic residues in a model HP-36 protein: relationship between contact order parameter and rate of folding and collapse

Abstract

Recent analysis of the structures of a large number of proteins in their native state has demonstrated a close relation between relative contact order parameter (COP) (which gives the average contact distance among hydrophobic residues) and the rate of protein folding (Grantcharova et al. Curr. Opin. Struct. Biol. 2001, 11, 70). We have explored the existence of such a relationship by carrying out Brownian dynamics simulations of a model protein. The model consists of 36 amino acid residues and mimics a thermostable single domain headpiece of chicken villin (HP-36) protein. Long range interactions across the protein are obtained by using a simplified hydropathy scale. The heteropolymer exhibits qualitative features of folding and correlates with the COP. We have defined and calculated the distance dependent pair correlation function among the hydrophobic residues. Nativelike states are characterized by distinct pair contacts which are mostly absent in other collapsed non-native states. Contact pair formation shows a strong dependence on contour distance separation between the pairs. Study of the dynamics of specific contact pair formation during folding shows different characteristics depending on whether the final state is (near) native or far from the native configuration. Approach to the final collapsed state is almost always faster when the final state is nativelike. Fluctuations in pair contacts are found to be smaller in nativelike conformations compared to those of higher energy configurations. This is in agreement with a recent theoretical prediction.