Determination of the backbone mobility of ribonuclease T1 and its 2'GMP complex using molecular dynamics simulations and NMR relaxation data

J Biomol Struct Dyn. 1994 Jun;11(6):1377-402. doi: 10.1080/07391102.1994.10508074.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Crystallography, X-Ray
  • Guanosine Monophosphate / chemistry*
  • Guanosine Monophosphate / metabolism
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Protein Structure, Secondary*
  • Ribonuclease T1 / chemistry*
  • Ribonuclease T1 / metabolism
  • Water / chemistry

Substances

  • Water
  • 2'-guanylic acid
  • Guanosine Monophosphate
  • Ribonuclease T1