Equilibrium properties of realistic random heteropolymers and their relevance for globular and naturally unfolded proteins

TL;DR

This paper investigates the equilibrium properties of realistic random heteropolymers using advanced sampling techniques, revealing different behaviors depending on the average monomer interactions, with implications for understanding protein states.

Contribution

It introduces a self-adjusting parallel-tempering method for continuous-space heteropolymers and analyzes their equilibrium states beyond mean-field models.

Findings

Negative mean interactions lead to near-random energy model behavior.

Positive mean interactions result in behavior akin to Ising spin glasses.

Different interaction signs correspond to denatured and unfolded protein states.

Abstract

Random heteropolymers do not display the typical equilibrium properties of globular proteins, but are the starting point to understand the physics of proteins and, in particular, to describe their non-native states. So far, they have been studied only with mean-field models in the thermodynamic limit, or with computer simulations of very small chains on lattice. After describing a self-adjusting parallel-tempering technique to sample efficiently the low-energy states of frustrated systems without the need of tuning the system-dependent parameters of the algorithm, we apply it to random heteropolymers moving in continuous space. We show that if the mean interaction between monomers is negative, the usual description through the random energy model is nearly correct, provided that it is extended to account for non-compact conformations. If the mean interaction is positive, such a simple description breaks out and the system behaves in a way more similar to Ising spin glasses. The former case is a model for the denatured state of glob- ular proteins, the latter of naturally-unfolded proteins, whose equilibrium properties thus result qualitatively different.