title: Migration of small ligands in globins: Xe diffusion in truncated hemoglobin N.
abstract: In heme proteins, the efficient transport of ligands such as NO or O2 to the binding site is achieved via ligand migration networks. A quantitative assessment of ligand diffusion in these networks is thus essential for a better understanding of the function of these proteins. For this, Xe migration in truncated hemoglobin N (trHbN) of Mycobacterium Tuberculosis was studied using molecular dynamics simulations. Transitions between pockets of the migration network and intra-pocket relaxation occur on similar time scales (10 ps and 20 ps), consistent with low free energy barriers (1-2 kcal/mol). Depending on the pocket from where Xe enters a particular transition, the conformation of the side chains lining the transition region differs which highlights the coupling between ligand and protein degrees of freedom. Furthermore, comparison of transition probabilities shows that Xe migration in trHbN is a non-Markovian process. Memory effects arise due to protein rearrangements and coupled dynamics as Xe moves through it.
authors.affiliation: Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Polydefkis
authors.identifier: 0000-0003-0535-3158
authors.initials: P
authors.lastname: Diamantis
authors.affiliation: Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Unke
authors.affiliation: Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Meuwly
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology; D018360:Crystallography, X-Ray; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D054793:Truncated Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D014978:Xenon / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006455:Hemoglobins, Abnormal; D008024:Ligands; D054793:Truncated Hemoglobins; D014978:Xenon; C031031:hemoglobins N