CONICET | Buscador de Institutos y Recursos Humanos

The energy landscape of natively folded proteins is minimally frustrated. This property obeys the necessity of proteins to fold and fulfill their functional role in biological times.The energy difference between native and non-native conformations, the "energy gap", determines the foldability of proteins. This energy gap is the product of evolutionary processes that selected sequences that best fit the structure, function and dynamics of each protein. The concept of minimal frustration assumes that the strength and consistency of native interactions between residues is much higher than non-native interactions. The probability of proteins to escape from non-native energy traps in the folding process depends on the stability of the local trap and the temperature of the environment. Therefore, it is possible that proteins adapted to fold and function in organisms that live at different temperature conditions, would tolerate different levels of frustration in their energy landscape. In this work we explore the global and local frustration of proteins from extremophile organisms. We evaluate parameters related to the foldability and conformational flexibility of these proteins. For this aim, we use protein homologs from psychrophilic, mesophilic and thermophilic organisms with structure solved at highresolution. We calculate the energetic frustration of these proteins with the ?frustratometer2.0? program that uses the coarse grained force field potential of the AWSEM program, designed for protein structure prediction. The results illustrate the challenges of this analysis and suggest possible explanations to the expected necessity of improvingfoldability and increasing flexibility of the native state at decreasing temperatures.