Factors that Affect the Folding Ability of Proteins

TL;DR

This study demonstrates that the protein folding ability correlates strongly with the energy gap between native and dissimilar states, and introduces robust, simulation-independent estimates as better predictors than traditional parameters.

Contribution

The paper identifies energy gap estimates as more reliable predictors of folding ability than the commonly used parameter , challenging the interpretation of  as a collapse transition indicator.

Findings

Energy gap correlates strongly with folding ability.

Energy gap estimates outperform  in predicting folding.

Interpretation of  as collapse temperature is generally incorrect.

Abstract

The folding ability of a heteropolymer model for proteins subject to Monte Carlo dynamics on a simple cubic lattice is shown to be strongly correlated with the energy gap between the native state and the structurally dissimilar part of the spectrum. We consider a number of estimates of the energy gap that can be determined without simulation, including the gap in energy between the native and first excited fully compact states for sequences with fully compact native states. These estimates are found to be more robust predictors of folding ability than a parameter $\sigma$ that requires simulation for its evaluation: $\sigma = 1 - T_f/T_\theta$, where $T_f$ is the temperature at which the fluctuation of the order parameter is at its maximum and $T_\theta$ is the temperature at which the specific heat is at its maximum. We show that the interpretation of $T_\theta$ as the collapse transition temperature is not correct in general and that the correlation between $\sigma$ and the folding ability arises from the fact that $\sigma$ is essentially a measure of the energy gap.