title: Structural Interpretation of Metastable States in Myoglobin-NO.
abstract: Nitric oxide binding and unbinding from myoglobin (Mb) is central to the function of the protein. By using reactive molecular dynamics (MD) simulations, the dynamics following NO dissociation were characterized in both time and space. Ligand rebinding can be described by two processes on the 10 ps and 100 ps timescale, which agrees with recent optical and X-ray absorption experiments. Explicitly including the iron out-of-plane (Fe-oop) coordinate is essential for a meaningful interpretation of the data. The proposed existence of an "Fe-oop/NO-bound" state is confirmed and assigned to NO at a distance of approximately 3 Å away from the iron atom. However, calculated XANES spectra suggest that it is diffcult to distinguish between NO close to the heme-Fe and positions further away in the primary site. Another elusive state, with Fe-ON coordination, was not observed experimentally because it is masked by the energetically more favorable but dissociative (4) A state in this region, which makes the Fe-ON local minimum unobservable in wild-type Mb. However, suitable active-site mutations may stabilize this state.
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056, Basel, Switzerland.
authors.forename: Maksym
authors.initials: M
authors.lastname: Soloviov
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056, Basel, Switzerland.
authors.forename: Akshaya K
authors.initials: AK
authors.lastname: Das
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056, Basel, Switzerland. m.meuwly@unibas.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Meuwly
mesh_terms: D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D009211:Myoglobin; D009569:Nitric Oxide
keywords: metastable states; myoglobin; nitric oxide; reactive molecular dynamics