title: Ligand migration through hemeprotein cavities: insights from laser flash photolysis and molecular dynamics simulations.
abstract: The presence of cavities and tunnels in the interior of proteins, in conjunction with the structural plasticity arising from the coupling to the thermal fluctuations of the protein scaffold, has profound consequences on the pathways followed by ligands moving through the protein matrix. In this perspective we discuss how quantitative analysis of experimental rebinding kinetics from laser flash photolysis, trapping of unstable conformational states by embedding proteins within the nanopores of silica gels, and molecular simulations can synergistically converge to gain insight into the migration mechanism of ligands. We show how the evaluation of the free energy landscape for ligand diffusion based on the outcome of computational techniques can assist the definition of sound reaction schemes, leading to a comprehensive understanding of the broad range of chemical events and time scales that encompass the transport of small ligands in hemeproteins.
authors.affiliation: Dipartimento di Fisica e Scienze della Terra, Università degli Studi di Parma, viale delle Scienze 7A, 43124, Parma, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Abbruzzetti
authors.forename: Francesca
authors.initials: F
authors.lastname: Spyrakis
authors.forename: Axel
authors.initials: A
authors.lastname: Bidon-Chanal
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Luque
authors.forename: Cristiano
authors.initials: C
authors.lastname: Viappiani
mesh_terms: D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D010782:Photolysis; D058428:Silica Gel / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D006420:Hemeproteins; D008024:Ligands; D058428:Silica Gel