IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Computational characterization of non-common iron III binding sites
Autor/es:
AGUDELO, WILLIAM A.; DIEGO S. VAZQUEZ; GONZÁLEZ FLECHA, F. LUIS; SANTOS, JAVIER; GONZALEZ LEBRERO, MARIANO CAMILO
Lugar:
Villa Carlos Paz, Córdoba
Reunión:
Congreso; XLI Reunión anual de la Sociedad Argentina de Biofísica.; 2013
Institución organizadora:
Sociedad Argentina de Biofísica
Resumen:
The motif (E/D)(E/D)xx(E/D)(E/D) is involved in iron exchange in the CyaY protein family and it is present in other metal ion binding proteins. Based on the C-terminal α-helix of E. coli thioredoxin a model peptide containing the motif was synthesized and studied. This peptide shows iron III binding and induction of α-helical structure*. However the microscopic details of the motif-ion interactions are unknown. In this work the system was addressed by computational simulation techniques. The main goal was the characterization of possible structures of metal peptide complex. To obtain suitable peptide-ion structures, geometrical search was performed by genetic algorithm and the most promising candidates were filtered by geometric criteria. Afterward, selected complexes were submitted to molecular dynamics simulations and the binding free energies were computed by thermodynamic Integration and compared with experimental results from isothermal titration calorimetry*. In addition, the protonation state of each residue of the motif was explored in the absence of the metal ion to evaluate a possible effect of clustering negatively charged residues on individual pKa values. * See submitted abstract: Vazquez DS et al., ?Grafting a functional iron-binding motif onto a thioredoxin scaffold?.