Molecular Insights of Heme Proteins by means of Free Energy Calculations

LUCIANA CAPECE; DAMIAN A. BIKIEL; ALEJANDRO D. NADRA; LEONARDO BOECHI; MARCELO A. MARTI; AXEL BIDON-CHANAL; F. JAVIER LUQUE; DARIO A. ESTRIN

Paris

Workshop; Free Energy Calculations: From Theory to Applications; 2012

CECAM

P { margin-bottom: 0.08in; } 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.