ESTRIN Dario Ariel
congresos y reuniones científicas
Computer simulation of ligand binding and reactivity of heme proteins
Genova, Italia
Conferencia; European Biophysical Society Meeting; 2009
Institución organizadora:
European Biophysical Society
<!-- @page { size: 21cm 29.7cm; margin: 2cm } P { margin-bottom: 0.21cm } --> We present an investigation of the molecular basis of ligand binding and reactivity of heme proteins using computer simulation. A combination of classical molecular dynamics and hybrid quantum-classical (QM-MM) calculations are applied to explore distal and proximal effects on diatomic ligand binding to the heme. Trends in binding energies and in the kinetic constants are illustrated through a number of selected examples. We present also an investigation of the interplay between ligand migration and protein dynamics obtained through classical molecular dynamics (MD) techniques in combination with advanced sampling tools. These techniques yield significant information about free energy profiles and possible secondary docking sites. Results for the deoxy and oxy truncated N hemoglobin of Mycobacterium Tuberculosis, presented as an illustrative example, suggest that the truncated hemoglobin N has evolved a dual-path mechanism for selective/distinct migration of O2 and NO to  he heme, to achieve efficient NO detoxification. Finally, we present also an analysis of the molecular basis of hexacoordination in human neuroglobin, which suggest that the flexibility of the CD plays a key role in determining the ligand binding properties.