IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Relationship between a complementation model of E. coli TRX and unfolding pathway intermediates studied by molecular dynamics.
Autor/es:
MAURICIO P. SICA; JAVIER SANTOS
Lugar:
Salta, Argentina
Reunión:
Congreso; Annual Meeting of the Argentinean Biophysical Society 2010. 3rd. Latin American Protein Society Meeting.; 2010
Institución organizadora:
Latin American Protein Society Meeting.
Resumen:
The interaction in solution between the fragments 1-93 and 94-108 from thioredoxin of E.coli has been a valuable model in the study of the mechanism of terciary structure consolidation. In order to have some insight about the relation between this model and the folding pathway of this proteins, we have applied all (heavy)-atom, structure based molecular dynamics simulations. These simulations, that are based on Go-model force fields, produce smoother energy landscapes which enable much longer simulation times scales compared to conventional force fields. We perform several independent simulations at different temperatures sapnning values where the protein is allways folded to values where it is allways unfolded. With these simulations in conjunction we postulate a folding mechanism. Several intermediates are observed in this mechanis. But, remarkably, the early events in the the unfolding pathway involve the denatuation of helix 94-108. As reported in the experimental model, this conveys the disruption of interaction with the helix corresponding to residues 35-50. Also, along the pathway, several intermediate conformations are observed corresponding to other complementation models reported in the literature. The results of our simulations reveal that the complementation model studied here reflects fundamental aspects of the folding mechanism of this protein.