Structural dynamics of members of the CyaY family

ERNESTO A. ROMAN; PATRICIO O. CRAIG; JAVIER SANTOS

San Javier, Tucumán, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

The structural dynamics of proteins is crucial for their function. A balancebetween stability and flexibility exist for their optimal functionality. Theanalysis of the local stability distribution, the description of alternativeconfigurations near the native basin, and their interconvertion rates, isessential for understanding the role of proteins in the biological processesthey are involved. In this work, we characterized CyaY protein familymotions as studied by molecular dynamic simulations. We studied threemembers of this family, and one home-made variant: I) Homosapiens frataxin, II) its C-terminus-truncated variant, III) Escherichiacoli frataxin, and IV) Psychromonas ingrahamii frataxin. We found that themost mobile regions are the ones corresponding to a) the first N-terminusloop (position ~20-30 in all sequences), b) the 
5-
6 loop (position ~66-80), and c) the C-terminus (position ~105-120). The local flexibilityobserved in the simulations is compared to crystallographic B factors andthe distribution of local energetic frustration (using all atom and coarsegrained potentials). In addition, we investigated local stabilities usingCOREX/BEST calculations. We expect that our results contribute to theunderstanding of the relation between sequence, flexibility, and stability.Further experiments and analysis would aid in the rational tuning of proteinfunction.