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Are coarse-grained models apt to detect protein thermal stability? the case of OPEP force field

Research output: Contribution to journalArticleScientificpeer-review


Original languageEnglish
Pages (from-to)494-501
Number of pages8
JournalJournal of Non-Crystalline Solids
Publication statusPublished - 1 Jan 2015
Publication typeA1 Journal article-refereed


We present the first investigation of the kinetic and thermodynamic stability of two homologous thermophilic and mesophilic proteins based on the coarse-grained model OPEP. The object of our investigation is a pair of G-domains of relatively large size, 200 amino acids each, with an experimental stability gap of about 40 K. The OPEP force field is able to maintain stable the fold of these relatively large proteins within the hundred-nanosecond time scale without including external constraints. This makes possible to characterize the conformational landscape of the folded protein as well as to explore the unfolding. In agreement with all-atom simulations used as a reference, we show that the conformational landscape of the thermophilic protein is characterized by a larger number of substates with slower dynamics on the network of states and more resilient to temperature increase. Moreover, we verify the stability gap between the two proteins using replica-exchange simulations and estimate a difference between the melting temperatures of about 23 K, in fair agreement with experiment. The detailed investigation of the unfolding thermodynamics allows to gain insight into the mechanism underlying the enhanced stability of the thermophile relating it to a smaller heat capacity of unfolding.


  • Coarse-grained force field, Conformational substates network, Molecular dynamics, Protein thermodynamic stability, Thermophilic proteins