Coarse grained analysis of the connection between stability, flexibility and foldability of Adenylate Kinase variants from extremophile organisms

MATIAS SAFRANCHIK; ERNESTO A. ROMAN; MATIAS IGLESIAS-RANDO; PATRICIO O. CRAIG

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

The study of homologous proteins from extremophile organisms represents an excellentsystem to evaluate the functional dynamics of proteins and their dependence ontemperature. In this work we develop a bioinformatic analysis method to evaluate howthe stability and conformational flexibility of extremophile variants is related to theirfoldability and energy frustration. To evaluate the quality of the molecular interactions ofthe protein variants we used the coarse grained force field of the AWSEM program. Theuse of this force field also allow us to perform folding simulations of the proteins, andevaluate the thermodynamic profiles of their landscape. The stability, flexibility andfoldability analysis of the protein variants was done using two different approaches: 1)An approximate and fast approach using the frustratometer-2.0 program, which isadaptable to the analysis of large databases; 2) An specific and more accurate approachusing coarse-grained computer simulations using the program AWSEM-MD. Here wepresent the results obtained for adenylate kinase homologs from psychrophilic (Bacillusglobisporus), mesophilic (Bacillus subtilis) and thermophilic (Bacillus stearothermophilus)organisms. The results illustrate the challenges of this analysis and suggest possibleexplanations for the expected necessity of improving foldability and flexibility of proteinsadapted to low temperatures.