Cooperativity in Protein Folding: From Lattice Models with Side Chains to Real Proteins

TL;DR

This paper introduces a measure of cooperativity in protein folding, demonstrating that lattice models with side chains better replicate real protein behavior and that a single parameter, sigma, effectively predicts folding cooperativity.

Contribution

The study defines a new quantitative measure, Omega_c, for cooperativity, and shows its strong correlation with sigma, linking theoretical models with experimental protein folding data.

Findings

Omega_c is higher in lattice models with side chains.

Omega_c correlates strongly with sigma in both models and real proteins.

Sigma can predict the degree of folding cooperativity from experimental data.

Abstract

We consider equilibrium folding transitions in lattice protein models with and without side chains. A dimensionless measure, $Omega_{c}$, is introduced to quantitatively assess the degree of cooperativity in lattice models and in real proteins. We show that larger values of $\Omega_{c}$ resembling those seen in proteins are obtained in lattice models with side chains (LMSC). The enhanced cooperativity in LMSC is due to the possibility of denser packing of side chains in the interior of the model protein. We also establish that $\Omega_{c}$ correlates extremely well with (\sigma = (T_{\theta} -T_{f} )/T_{\theta}), where (T_{\theta}) and (T_{f}) are collapse and folding transition temperatures, respectively. These theoretical ideas are used to analyze folding transitions in various real proteins. The values of $\Omega _{c}$ extracted from experiments show a correlation with $\sigma $. We conclude that the degree of cooperativity can be expressed in terms of the single parameter $\sigma $, which can be estimated from experimental data.