Nitric oxide reactivity with globins as investigated through computer simulation.
This chapter reviews the application of classical and quantum-mechanical atomistic simulation tools used in the investigation of several relevant issues in nitric oxide reactivity with globins and presents different simulation strategies based on classical force fields: standard molecular dynamics, essential dynamics, umbrella sampling, multiple steering molecular dynamics, and a novel technique for exploring the protein energy landscape. It also presents hybrid quantum-classical schemes as a tool to obtain relevant information regarding binding energies and chemical reactivity of globins. As illustrative examples, investigations of the structural flexibility, ligand migration profiles, oxygen affinity, and reactivity toward nitric oxide of truncated hemoglobin N of Mycobacterium tuberculosis are presented.
Marti
Marcelo A
MA
Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
Capece
Luciana
L
Bidon-Chanal
Axel
A
Crespo
Alejandro
A
Guallar
Victor
V
Luque
F Javier
FJ
Estrin
Dario A
DA
D001696:Biomechanical Phenomena; D003198:Computer Simulation; D004734:Energy Metabolism; D005914:Globins / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000737:chemistry; D008658:Inactivation, Metabolic; D007700:Kinetics; D008958:Models, Molecular; D008962:Models, Theoretical; D009169:Mycobacterium tuberculosis; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D017510:Protein Folding; D011789:Quantum Theory; D015398:Signal Transduction; D013379:Substrate Specificity; D054793:Truncated Hemoglobins / Q000737:chemistry
D009211:Myoglobin; D054793:Truncated Hemoglobins; D009569:Nitric Oxide; D006418:Heme; D005914:Globins; D010100:Oxygen