Backbone and Sidechain Ordering in a small Protein

TL;DR

This study uses multicanonical simulations to analyze the relationship between backbone and side-chain ordering in a small protein, revealing a thermal hierarchy of ordering events without distinct collective transitions.

Contribution

It introduces circular statistics to analyze side-chain fluctuations and demonstrates that side-chain ordering occurs over a broad temperature range, challenging previous findings of separate transitions.

Findings

Side-chain ordering occurs over a wide temperature range.

No evidence of a separate collective transition for side-chains.

Side-chain ordering precedes the folding transition.

Abstract

We investigate the relation between backbone and side-chain ordering in a small protein. For this purpos e we have performed multicanonical simulations of the villin headpiece subdomain HP-36, an often used to y model in protein studies. Concepts of circular statistics are introduced to analyze side-chain fluctuations. In contrast to earlier studies on homopolypeptides (Wei et al., J. Phys. Chem. B, 111 (2007) 4244) we do not find collective effects leading to a separate transition. Rather, side-chain ordering is spread over a wide temperature range. Our results indicate a thermal hierarchy of ordering events, with side-chain ordering appearing at temperatures below the helix-coil transition but above the folding transition. We conjecture that this thermal hierarchy reflects an underlying temporal order, and that side-chain ordering facilitates the search for the correct backbone topology.