title: Breathing motions of a respiratory protein revealed by molecular dynamics simulations.
abstract: Internal cavities, which are central to the biological functions of myoglobin, are exploited by gaseous ligands (e.g., O(2), NO, CO, etc.) to migrate inside the protein matrix. At present, it is not clear whether the ligand makes its own way inside the protein or instead the internal cavities are an intrinsic feature of myoglobin. To address this issue, standard molecular dynamics simulations were performed on horse-heart met-myoglobin with no ligand migrating inside the protein matrix. To reveal intrinsic internal pathways, the use of a statistical approach was applied to the cavity calculation, with special emphasis on the major pathway from the distal pocket to Xe1. Our study points out the remarkable dynamical behavior of Xe4, whose "breathing motions" may facilitate migration of ligands through the distal region. Additionally, our results highlight a two-way path for a ligand to diffuse through the proximal region, possibly allowing an alternative route in case Xe1 is occupied. Finally, our approach has led us to the identification of key residues, such as leucines, that may work as switches between cavities.
authors: Department of Chemical Sciences, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato (Ca), Italy.
authors: Mariano Andrea
authors: MA
authors: Scorciapino
authors: Arturo
authors: A
authors: Robertazzi
authors: Mariano
authors: M
authors: Casu
authors: Paolo
authors: P
authors: Ruggerone
authors: Matteo
authors: M
authors: Ceccarelli
mesh_terms: D000818:Animals; D008024:Ligands; D008786:Metmyoglobin / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009068:Movement; D011487:Protein Conformation
chemical_list: D008024:Ligands; D008786:Metmyoglobin