Miotto, MattiaOlimpieri, Pier PaoloDi Rienzo, LorenzoAmbrosetti, FrancescoCorsi, PietroLepore, RosalbaTartaglia, Gian GaetanoMilanetti, Edoardo2019-10-292019-10-292019Miotto M, Olimpieri PP, Di Rienzo L, Ambrosetti F, Corsi P, Lepore R, Tartaglia GG, Milanetti E. Insights on protein thermal stability: a graph representation of molecular interactions. Bioinformatics. 2019; 35(15):2569-2577. DOI 10.1093/bioinformatics/bty10111367-4803http://hdl.handle.net/10230/42543Motivation: Understanding the molecular mechanisms of thermal stability is a challenge in protein biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, which 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. Results: Here, we present a novel graph-theoretical framework to assess thermal stability based on the structure without any a priori information. In this approach we describe proteins as energy-weighted graphs and compare them using ensembles of interaction networks. Investigating the position of specific interactions within the 3D native structure, we developed a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and area under the receiver operating characteristic curve of 78%. Availability and implementation: Code is available upon request to edoardo.milanetti@uniroma1.it Supplementary information: Supplementary data are available at Bioinformatics online.application/pdfeng© The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.cominfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/bioinformatics/bty1011info:eu-repo/semantics/openAccess