title: Determination of the backbone mobility of ribonuclease T1 and its 2'GMP complex using molecular dynamics simulations and NMR relaxation data.
abstract: The results of 1-nanosecond molecular dynamics simulations of the enzyme ribonuclease T1 and its 2'GMP complex in water are presented. A classification of the angular reorientations of the backbone amide groups is achieved via a transformation of NH-vector trajectories into several coordinate frames, thus unravelling contributions of NH-bond librations and backbone dihedral angle fluctuations. The former turned out to be similar for all amides, as characterized by correlation times of librational motions in a subpicosecond scale, angular amplitudes of about 10-12 degrees for out-of-peptide-plane displacements of the NH-bond and 3-5 degrees for the in-plane displacements, whereas the contributions of much slower backbone dihedral angle fluctuations strongly depend on the secondary structure. Correlation functions relevant for NMR were obtained and analyzed utilizing the 'model-free' approach (Lipari, G. and Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559, 4559-4570; Clore et al., (1990) J. Am. Chem. Soc. 112, 4989-4991). The dependence of the amplitude of local motion on the residue location in the backbone is in good agreement with the results of NMR relaxation measurements and X-ray data. The protein dynamics is characterized by a highly restricted local motion of those parts of the backbone with defined secondary structure as well as by a high flexibility in loop regions. The comparison of results derived from different periods of the trajectory (of 50 ps and 1 ns duration, 1000 points sampled) reveals a dependence of the observed dynamic picture on the characteristic time scale of the experimental method used. Comparison of the MD data for the free and liganded enzyme clearly indicates a restriction of the mobility within certain regions of the backbone upon inhibitor binding.
authors.affiliation: Institut für Biophysikalische Chemie der J.W. Goethe-Universität Frankfurt, Frankfurt am Main.
authors.forename: D
authors.initials: D
authors.lastname: Fushman
authors.forename: O
authors.initials: O
authors.lastname: Ohlenschläger
authors.forename: H
authors.initials: H
authors.lastname: Rüterjans
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006157:Guanosine Monophosphate / Q000737:chemistry* / Q000378:metabolism; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D006163:Ribonuclease T1 / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; C026693:2'-guanylic acid; D006157:Guanosine Monophosphate; D006163:Ribonuclease T1