Vibrational entropy and the structural organization of proteins

TL;DR

This study introduces the Hierarchical Network Model to analyze protein vibrational spectra, revealing correlations between vibrational entropy and secondary structure, with implications for understanding protein aggregation.

Contribution

The paper presents a novel hierarchical network model that accounts for heterogeneity in force constants and side-chain degrees of freedom in proteins.

Findings

Vibrational entropy per residue correlates with secondary structure content.

The hierarchical model improves predictions over existing network models.

Properly modeling force hierarchy is crucial for understanding protein stability.

Abstract

In this paper we analyze the vibrational spectra of a large ensemble of non-homologous protein structures by means of a novel tool, that we coin the Hierarchical Network Model (HNM). Our coarse-grained scheme accounts for the intrinsic heterogeneity of force constants displayed by protein arrangements and also incorporates side-chain degrees of freedom. Our analysis shows that vibrational entropy per unit residue correlates with the content of secondary structure. Furthermore, we assess the individual contribution to vibrational entropy of the novel features of our scheme as compared with the predictions of state-of-the-art network models. This analysis highlights the importance of properly accounting for the intrinsic hierarchy in force strengths typical of the different atomic bonds that build up and stabilize protein scaffolds. Finally, we discuss possible implications of our findings in the context of protein aggregation phenomena.