title: The conformational flexibility of 5,6,7,8-tetrahydrobiopterin and 5,6,7,8-tetrahydroneopterin: a molecular dynamical simulation.
abstract: 5,6,7,8-Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6R,1'R,2'S-configuration is biologically active. Other stereoisomers, as well as other reduced pterins such as, e.g. 5,6,7,8-tetrahydroneopterin, fail to exhibit significant cofactor activity. Different theoretical models (molecular mechanics, semi-empirical quantum chemical calculations) investigating the stereostructure of tetrahydrobiopterin have yielded diverging answers. It has been claimed on the basis of semi-empirical quantum chemical calculations that conformational properties, and thus particular features in overall shape, might be responsible for the unique biological properties of natural tetrahydrobiopterin in contrast, e.g. to 6R,1'S,2'R-5,6,7,8-tetrahydroneopterin. Molecular dynamical simulations of both molecules at realistic temperatures demonstrate, however, that they possess sufficient conformational flexibility as to render questionable any biological significance of mere conformational properties.
authors.affiliation: Medizinisch-Chemisches Institut und Pregl-Labor, Karl-Franzens-Universität Graz, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Estelberger
authors.forename: W
authors.initials: W
authors.lastname: Mlekusch
authors.forename: G
authors.initials: G
authors.lastname: Reibnegger
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry; D003198:Computer Simulation; D008958:Models, Molecular; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D001708:Biopterins; C023455:tetrahydroneopterin; C003402:sapropterin