pH-dependent Response of Coiled Coils: A Coarse-Grained Molecular Simulation Study

TL;DR

This study extends a coarse-grained simulation methodology to analyze how pH influences the folding, stability, and behavior of coiled coil proteins, comparing results with experimental data for validation.

Contribution

It introduces a model that accounts for chain length and rigidity to simulate pH-dependent coiled coil behavior, extending previous peptide interaction models.

Findings

pH affects coiled coil folding/unfolding transitions

model results align with experimental data for specific sequences

chain rigidity influences protein stability under different pH conditions

Abstract

In a recent work we proposed a coarse-grained methodology for studying the response of peptides when simulated at different values of pH; in this work we extend the methodology to analyze the pH-dependent behavior of coiled coils. This protein structure presents a remarkable chain stiffness andis formed by two or more long helical peptides that are interacting like the strands of a rope. Chain length and rigidity are the key aspects needed to extend previous peptide interaction potentials to this particular case; however the original model is naturally recovered when the length or the ridigity of the simulated chain are reduced. We apply the model and discuss results for two cases: (a) the folding/unfolding transition of a generic coiled coil as a function of pH; (b) behavior of a specific sequence as a function of the acidity conditions. In this latter case results are compared with experimental data from the literature in order to comment about the consistency of our approach.