Abstract
Understanding the molecular mechanisms of protein thermal stability is an important challenge in modern biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, that are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity.
Here, we present a novel graph-theoretical framework to assess thermal stability based on the protein structure without any a priori information. We describe proteins as energy-weighted interaction networks and compare them with ensembles of interaction networks. We investigated how evolution shapes the position of specific interactions within the 3D native structure. We present a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and Area Under the Roc Curve of 78%.
Footnotes
↵* Electronic address: gian{at}tartaglialab.com