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Groth, Małgorzata; Malicka, Joanna; Czaplewski, Cezary; Oldziej, S.; Łankiewicz, Leszek; Wiczk, Wiesław; Liwo, Adam

doi:10.1023/a:1008349424452

Cited by 38 publications

(34 citation statements)

References 29 publications

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“…These techniques permitted to calculate the structure of the minor conformation, which could not have been determined from NOE restraints. A maximum entropy method was used [332] to determine from MD trajectories an ensemble of flexible polypeptide conformation consistent with the experimental NMR measurements.…”

Section: Molecular Dynamics and Ensemble Refinementmentioning

confidence: 99%

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

Malliavin

2006

COC

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Nuclear Magnetic Resonance (NMR) became during the two last decades an important method for biomolecular structure determination. NMR permits to study biomolecules in solution and gives access to the molecular flexibility at atomic level on a complete structure: in that respect, it is occupying a unique place i n structural biology. During the first years of its development, NMR was trying to meet the requirements previously defined in X-ray crystallography. But, NMR then started to determine its own criteria for the definition of a structure. Indeed, the atomic coordinates of an NMR structure are calculated using restraints on geometrical parameters (angles and distances) of the structure, which are only indirectly related to atom positions: in that respect, NMR and X-ray crystallography are very different. The indirect relation between the NMR measurements and the molecular structure and dynamics makes critical the precision and the interpretation of the NMR parameters and the development of quantitative analysis methods. The methods published since 1997 for liquid-NMR of proteins are reviewed here. First, methods for structure determination are presented, as well as methods for spectral assignment and for structure quality assessment. Second, the quantitative analysis of structure mobility i s reviewed.

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Section: Molecular Dynamics and Ensemble Refinementmentioning

confidence: 99%

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

Malliavin

2006

COC

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“…We used a procedure described in our previous work. 17,34 This procedure, to describe it briefly, consists of the following two stages: (a) global theoretical conformational analysis of each of the peptides studied to obtain a complete (in theory) basis set of physically reasonable conformations and (b) fitting the statistical weights of the conformations to reproduce the NOE intensities and coupling constants. Global conformational search of the peptides studied was carried out using the electrostatically driven Monte Carlo method (EDMC) 28 -31 with the Empirical Conformational Energy Program for Peptides and Proteins (ECEPP/3) force field 35 augmented with the surface-…”

Section: Theoretical Calculationmentioning

confidence: 99%

“…To obtain conformational ensembles compatible with NMR data, we used our maximum-entropy fitting algorithm 17 implemented in the program ANALYZE. 38 In this method, the NOE intensities and coupling constants obtained from NMR measurements are considered as averages over conformations:…”

Section: Figurementioning

confidence: 99%

“…The statistical weights are determined to obtain the best fit between the theoretical and experimental NOE intensities and coupling constants, preserving the diversity of the conformational ensemble, which is characteristic of oligopeptides. 17 The target function to be minimized is thus composed of a sum-of-error-squares term and an entropy term 17 :…”

Section: Figurementioning

confidence: 99%

“…Subsequently, we carried out simulation of the NOE spectrum and vicinal coupling constants for each of the low-energy conformations and determined the statistical weights of the conformations, by means of the maximum-entropy method, 17 in order to obtain the best fit of the average NOE intensities and coupling constants to the experimental quantities.…”

Section: Introductionmentioning

confidence: 99%

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Conformational studies of cyclic enkephalin analogues with L‐ or D‐proline in position 3

et al. 2002

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The conformation of a series of cyclic enkephalin analogues of a general formula X(1)-cyclo[Y(2)-Z(3)-Nal(4)-Leu(5)] (Nal: beta-(2-naphthyl)alanine), where X = Tyr, Phe, or Phe(NO(2)), Y = D-Dab or L-Dab (Dab: 2,4-diaminobutyric acid), and Z = D-Pro or L-Pro, was studied by means of NMR spectroscopy and theoretical conformational analysis with the Empirical Conformational Energy Program for Peptides and Proteins force field plus solvation. The NMR measurements were performed in dimethyl sulfoxide solution. The nuclear Overhauser effect intensities and coupling constants were used to compute the statistical weights of the conformations of the ensemble generated in global conformational searches. The purpose of this study was to determine whether introducing the D- or L-proline residue in position 3 can produce peptides with both rigid backbone and significant separation of the pharmacophore groups in position 1 and 4 (as required for high affinity for the mu-type opioid receptors). It was found that the analogues with D-Dab in position 2 and D-Pro in position 3 possess a stable type II' beta-turn at positions 3 and 4, which rigidifies the cyclic backbone; this finding was confirmed by independent measurements of the temperature coefficients of the amide protons, which indicated very significant screening of the Leu(5) amide proton from the solvent. However, these analogues were found to possess a short interchromophore distance. The analogues containing both Dab and Pro in the L-configuration are characterized by a larger interchromophore distance; however, they do not possess a stable beta-turn and have therefore a higher conformational flexibility. The modifications proposed in this work are therefore not likely to lead to enkephalin analogues with a high affinity for the mu-receptors.

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Determination of conformational equilibrium of peptides in solution by NMR spectroscopy and theoretical conformational analysis: Application to the calibration of mean-field solvation models

Groth

Malicka

et al. 2001

Biopolymers

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Peptides occur in solution as ensembles of conformations rather than in a fixed conformation. The existing energy functions are usually inadequate to predict the conformational equilibrium in solution, because of failure to account properly for solvation, if the solvent is not considered explicitly (which is usually prohibitively expensive). NMR data are therefore widely incorporated into theoretical conformational analysis. Because of conformational flexibility, restrained molecular dynamics (with restraints derived from NMR data), which is usually applied to determine protein conformation is of limited use in the case of peptides. Instead, (a) the restraints are averaged within predefined time windows during molecular dynamics (MD) simulations (time averaging), (b) multiple‐copy MD simulations are carried out and the restraints are averaged over the copies (ensemble averaging), or (c) a representative ensemble of sterically feasible conformations is generated and the weights of the conformations are then fitted so that the computed average observables match the experimental data (weight fitting). All these approaches are briefly discussed in this article. If an adequate force field is used, conformations with large statistical weights obtained from the weight‐fitting procedure should also have low energies, which can be implemented in force field calibration. Such a procedure is particularly attractive regarding the parameterization of the solvation energy in nonaqueous solvents, e.g., dimethyl sulfoxide, for which thermodynamic solvation data are scarce. A method for calibration of solvation parameters in dimethyl sulfoxide, which is based on this principle was recently proposed by C. Baysal and H. Meirovitch (Journal of the American Chemical Society, 1998, Vol. 120, pp. 800–812), in which the energy gap between the conformations compatible with NMR data and the alternative conformations is maximized. In this work we propose an alternative method based on the principle that the best‐fitting statistical weights of conformations should match the Boltzmann weights computed with the force field applied. Preliminary results obtained using three test peptides of varying conformational mobility: H–Ser1–Pro2–Lys3–Leu4–OH, Ac–Tyr1–D‐Phe2–Ser3–Pro4–Lys5–Leu6–NH2, and cyclo(Tyr1–D‐Phe2–Ser3–Pro4–Lys5–Leu6) are presented. © 2001 John Wiley & Sons, Inc. Biopolymers (Pept Sci) 60: 79–95, 2001

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Untitled

Cited by 38 publications

References 29 publications

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

Conformational studies of cyclic enkephalin analogues with L‐ or D‐proline in position 3

Determination of conformational equilibrium of peptides in solution by NMR spectroscopy and theoretical conformational analysis: Application to the calibration of mean-field solvation models

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