title: Dioxygen affinity in heme proteins investigated by computer simulation.
abstract: We present an investigation of the molecular basis of the modulation of oxygen affinity in heme proteins using computer simulation. QM-MM calculations are applied to explore distal and proximal effects on O(2) binding to the heme, while classical molecular dynamics simulations are employed to investigate ligand migration across the polypeptide to the active site. Trends in binding energies and in the kinetic constants are illustrated through a number of selected examples highlighting the virtues and the limitations of the applied methodologies. These examples cover a wide range of O(2)-affinities, and include: the truncated-N and truncated-O hemoglobins from Mycobacterium tuberculosis, the mammalian muscular O(2) storage protein: myoglobin, the hemoglobin from the parasitic nematode Ascaris lumbricoides, the oxygen transporter in the root of leguminous plants: leghemoglobin, the Cerebratulus lacteus nerve tissue hemoglobin, and the Alcaligenes xyloxidans cytochrome c'.
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/Inquimae-Conicet, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Marti
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
authors.forename: Luciana
authors.initials: L
authors.lastname: Capece
authors.forename: Leonardo
authors.initials: L
authors.lastname: Boechi
authors.forename: Damián E
authors.initials: DE
authors.lastname: Bikiel
authors.forename: Damián A
authors.initials: DA
authors.lastname: Scherlis
authors.forename: Dario A
authors.initials: DA
authors.lastname: Estrin
mesh_terms: D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; D008024:Ligands; D009211:Myoglobin; D010100:Oxygen