INVESTIGADORES
CAPECE Luciana
congresos y reuniones científicas
Título:
Molecular Insights of Heme Proteins by means of Free Energy Calculations
Autor/es:
LUCIANA CAPECE; DAMIAN A. BIKIEL; ALEJANDRO D. NADRA; LEONARDO BOECHI; MARCELO A. MARTI; AXEL BIDON-CHANAL; F. JAVIER LUQUE; DARIO A. ESTRIN
Lugar:
Paris
Reunión:
Workshop; Free Energy Calculations: From Theory to Applications; 2012
Institución organizadora:
CECAM
Resumen:
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Heme
proteins are present in all living organisms and perform a wide range
of functions. All these proteins present a heme group in their active
site. The iron in the heme group posses six coordination positions,
four of them occupied by the pyrrolic nytrogen atoms of the
porphyrin. The other two coordination sites are called proximal and
distal site. The distal site, is commonly where the exogenous
ligands bind to the protein and allow it to perform its function.
Binding of ligands in heme proteins is determined by the migration
through protein channels and/or opening of specific gates, the
accessibility of the distal site and the stabilization of the ligand
once bound to the heme.
Here
we combine classical molecular dynamics simulations and hybrid
Quantum Mechanics - Molecular Mechanics (QM/MM) with advanced
sampling techniques (i.e. Umbrella Sampling, Multiple Steered
Molecular Dynamics) to study key aspects of heme proteins:
-
Multiple conformations and conformational changes.
-
Ligand migration through internal channels, opening and closing of
gates.
-
Heme Coordination
-
Binding Energy
-
Effect of point mutations
-Reactivity,
Catalysis, Reaction Mechanisms.
In
this poster we present three selected examples.