CONICET | Buscador de Institutos y Recursos Humanos

The study of homologous proteins from extremophile organisms represents an excellent system to evaluate the functional dynamics of proteins and their dependence on temperature. In this work we develop a bioinformatic analysis method to evaluate how the stability and conformational flexibility of extremophile variants is related to their foldability and energy frustration. To evaluate the quality of the molecular interactions of the protein variants we used the coarse grained force field of the AWSEM program. The use of this force field also allow us to perform folding simulations of the proteins, and evaluate the thermodynamic profiles of their landscape. The stability, flexibility and foldability analysis of the protein variants was done using two different approaches: 1) An approximate and fast approach using the Frustratometer-2.0program, which is adaptable to the analysis of large databases; 2)An specific and more accurate approach using coarse-grained computer simulations using the program AWSEM-MD. Here we present the results obtained for adenylate kinase homologs from psychrophilic (Bacillus globisporus), mesophilic (Bacillus subtilis) and thermophilic (Bacillus stearothermophilus) organisms. The results illustrate the challenges of this analysis and suggest possible explanations for the expected necessity of improving foldability and flexibility of proteins adapted to low temperatures.