A Monte Carlo simulation study of the influence of internal motions on the molecular conformation deduced from two‐dimensional nmr experiments

Monte Carlo methods have been used to simulate internal motions of aromatic protons of an oligonucleotide at the nanosecond time scale. Each proton is allowed to fluctuate about its equilibrium position. The longitudinal cross‐relaxation rates of such a system of spins have been determined by computing the appropriate correlation functions. Then the interproton distances have been deduced according to the procedure generally used in two‐dimensional nmr techniques (nuclear Overhauser effect spectroscopy—NOESY) and compared to the true values. The influence of the amplitude A and of the internal rotational diffusion constant Dint characterizing the dynamics of the system has been checked for in‐phase and for uncorrelated motions. It is shown that for the investigated models the distances deduced from NOESY experiments may be under or overestimated, depending strongly on the values of A and Dint. Furthermore, the cross‐relaxation rate of a couple of protons is very sensitive to the correlation level of the motions of both protons.

[1]  J. Tropp.  Dipolar relaxation and nuclear Overhauser effects in nonrigid molecules: The effect of fluctuating internuclear distances , 1980 .

[2]  T. James,et al.  A theoretical study of distance determinations from NMR. Two-dimensional nuclear overhauser effect spectra , 1984 .

[3]  R. R. Ernst,et al.  Two‐dimensional spectroscopy. Application to nuclear magnetic resonance , 1976 .

[4]  P. Wahl,et al.  Fluorescence anisotropy decay due to rotational brownian motion of ethidium intercalated in double strand DNA. , 1978, Biochimica et biophysica acta.

[5]  M. Ptak,et al.  Conformational study of bacterial lipopeptides: Refinement of the structure of iturin A in solution by two‐dimensional 1H‐nmr and energy calculations , 1986, Biopolymers.

[6]  A. Szabó,et al.  Theory of NMR relaxation in macromolecules: Restricted diffusion and jump models for multiple internal rotations in amino acid side chains , 1978 .

[7]  R. London,et al.  Calculation of carbon-13 relaxation times and nuclear Overhauser enhancements in a hydrocarbon chain undergoing gauche-trans isomerism , 1977 .

[8]  C. Altona,et al.  Conformational analysis of the B and Z forms of the d(m5C-G)3 and d(br5C-G)3 hexamers in solution. A 300-MHz and 500-MHz NMR study. , 1986, European journal of biochemistry.

[9]  Richard R. Ernst,et al.  Elucidation of cross relaxation in liquids by two-dimensional N.M.R. spectroscopy , 1980 .

[10]  K Wüthrich,et al.  Sequential resonance assignments as a basis for determination of spatial protein structures by high resolution proton nuclear magnetic resonance. , 1982, Journal of molecular biology.

[11]  D. Kearns,et al.  Investigation of DNA dynamics and drug-DNA interaction by steady state fluorescence anisotropy. , 1985, Nucleic acids research.

[12]  M. Nilges,et al.  Three-dimensional structure of phoratoxin in solution: combined use of nuclear magnetic resonance, distance geometry, and restrained molecular dynamics , 1987 .

[13]  D. Marion,et al.  Modelling and refinement of the conformation of mycosubtilin in solution from two-dimensional NMR data. , 1987, European journal of biochemistry.

[14]  H. Carr,et al.  The Principles of Nuclear Magnetism , 1961 .

[15]  O. Jardetzky,et al.  Internal motions in deoxyribonucleic acid II. , 1980, Biochemistry.

[16]  T. James,et al.  Models for DNA backbone motions: an interpretation of NMR relaxation experiments , 1982 .

[17]  A. Gronenborn,et al.  Refinement of the solution structure of the B DNA hexamer 5'd(C-G-T-A-C-G)2 on the basis of inter-proton distance data. , 1985, Journal of molecular biology.

[18]  M. Karplus,et al.  Motional averaging of proton nuclear Overhauser effects in proteins. Predictions from a molecular dynamics simulation of lysozyme , 1984 .

[19]  D. Woessner.  Nuclear Magnetic Dipole—Dipole Relaxation in Molecules with Internal Motion , 1965 .

[20]  W. Vangunsteren,et al.  CONFORMATIONAL DYNAMICS DETECTED BY NUCLEAR MAGNETIC-RESONANCE NOE VALUES AND J-COUPLING CONSTANTS , 1988 .

[21]  A. Gronenborn,et al.  A two-dimensional NMR study of the solution structure of a DNA dodecamer comprising the concensus sequence for the specific DNA-binding sites of the glucocorticoid receptor protein. , 1984, European journal of biochemistry.

[22]  B. S. Snowden,et al.  Nuclear Spin–Lattice Relaxation in Axially Symmetric Ellipsoids with Internal Motion , 1969 .

[23]  Horst Kessler,et al.  Peptide conformations. 46. Conformational analysis of a superpotent cytoprotective cyclic somatostatin analog , 1988 .

[24]  M. Guéron,et al.  Proton exchange and base-pair lifetimes in a deoxy-duplex containing a purine-pyrimidine step and in the duplex of inverse sequence. , 1987, Journal of molecular biology.