Normal modes and NMR order parameters in proteins

Brueschweiler, Rafael

doi:10.1021/ja00039a052

Cited by 44 publications

(39 citation statements)

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“…A small systematic difference (,0.02) between the E1/E2 and MD1/MD2 sets may be related to the neglect of the zero-point vibrational contribution in the MD trajectories. 21,50 We have shown further that the accuracy of MD S 2 values is (at least in this test case) comparable with that of NMR values: the widths of DS 2 distributions involving an NMR and MD set are, on the whole, similar to those of distributions between two NMR sets, and the degree of linear correlation between NMR and MD data sets is within the range of correlations observed for NMR data sets. This result justifies the predictive use of MD simulations for the characterization of backbone protein dynamics on a fast timescale (,100 ps).…”

Section: Resultssupporting

confidence: 63%

“…On the other hand, MD1 and MD2 S 2 values are systematically higher than those in E2f and E1f, as indicated by median values between 0.01 and 0.02, consistent with the neglect of zero-point energy in the classical simulations. 21,50 Notably, values of DS 2 greater than 0.1 for residues L2, D10, G30, S71, W81, G123, and A125-H127 in the intralab data sets, E1f and E2f, also occur in E1f-MD1, E1f-MD2, E2f-MD1, and E2f-MD2 (Figs. 1 and 2).…”

Section: Comparison Of Dynamic Models In the Three Nmr Sets And Corrementioning

confidence: 94%

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Accuracy and precision of NMR relaxation experiments and MD simulations for characterizing protein dynamics

et al. 1997

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Model-free parameters obtained from nuclear magnetic resonance (NMR) relaxation experiments and molecular dynamics (MD) simulations commonly are used to describe the intramolecular dynamical properties of proteins. To assess the relative accuracy and precision of experimental and simulated model-free parameters, three independent data sets derived from backbone 15N NMR relaxation experiments and two independent data sets derived from MD simulations of Escherichia-coli ribonuclease HI are compared. The widths of the distributions of the differences between the order parameters for pairs of NMR data sets are congruent with the uncertainties derived from statistical analyses of individual data sets; thus, current protocols for analyzing NMR data encapsulate random uncertainties appropriately. Large differences in order parameters for certain residues are attributed to systematic differences between samples for intralaboratory comparisons and unknown, possibly magnetic field-dependent, experimental effects for interlaboratory comparisons. The widths of distributions of the differences between the order parameters for two NMR sets are similar to widths of distributions for an NMR and an MD set or for two MD sets. The linear correlations between the order parameters for an MD set and an NMR set are within the range of correlations observed between pairs of NMR sets. These comparisons suggest that the NMR and MD generalized order parameters for the backbone amide N-H bond vectors are of comparable accuracy for residues exhibiting motions on a fast time scale (< 100 ps). Large discrepancies between NMR and MD order parameters for certain residues are attributed to the occurrence of "rare" motional events over the simulation trajectories, the disruption of an element of secondary structure in one of the simulations, and lack of consensus among the experimental data sets. Consequently, (easily detectable) severe distortions of local protein structure and infrequent motional events in MD simulations appear to be the most serious artifacts affecting the accuracy and precision, respectively, of MD order parameters relative to NMR values. In addition, MD order parameters for motions on a fast (< 100 ps) timescale are more precisely determined than their NMR counterparts, thereby permitting more detailed dynamic characterization of biologically important residues by MD simulation than is sometimes possible by experimental methods. Proteins 28:481-493, 1997.

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Section: Resultssupporting

confidence: 63%

Section: Comparison Of Dynamic Models In the Three Nmr Sets And Corrementioning

confidence: 94%

Accuracy and precision of NMR relaxation experiments and MD simulations for characterizing protein dynamics

et al. 1997

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“…The locations of the most mobile regions correlate well with the experimental NMR structure ensemble, 29 normal mode calculations, 43 and differences between the X-ray crystal structures in different crystal forms. 44 However, the fluctuations are significantly larger than those found in the experimental NMR ensemble (ref.…”

Section: Trajectory and Reference Structuresupporting

confidence: 61%

Molecular dynamics and accuracy of NMR structures: Effects of error bounds and data removal

1999

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The effect of internal dynamics on the accuracy of nuclear magnetic resonance (NMR) structures was studied in detail using model distance restraint sets (DRS) generated from a 6.6 nanosecond molecular dynamics trajectory of bovine pancreatic trypsin inhibitor. The model data included the effects of internal dynamics in a very realistic way. Structure calculations using different error estimates were performed with iterative removal of systematically violated restraints. The accuracy of each calculated structure was measured as the atomic root mean square (RMS) difference to the optimized average structure derived from the trajectory by structure factors refinement. Many of the distance restraints were derived from NOEs that were significantly affected by internal dynamics. Depending on the error bounds used, these distance restraints seriously distorted the structure, leading to deviations from the coordinate average of the dynamics trajectory even in rigid regions. Increasing error bounds uniformly for all distance restraints relieved the strain on the structures. However, the accuracy did not improve. Significant improvement of accuracy was obtained by identifying inconsistent restraints with violation analysis, and excluding them from the calculation. The highest accuracy was obtained by setting bounds rather tightly, and removing about a third of the restraints. The limiting accuracy for all backbone atoms was between 0.6 and 0.7 A. Also, the precision of the structures increased with removal of inconsistent restraints, indicating that a high precision is not simply the consequence of tight error bounds but of the consistency of the DRS. The precision consistently overestimated the accuracy.

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“…The sampling issue can be bypassed, at the cost of accuracy, by using normal-mode analysis where the force field in the vicinity of the native state is replaced by its multivariate quadratic expansion. This allows the compact representation of protein dynamics by the superposition of motional fluctuations along normal modes with individual amplitudes (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

All-Atom Contact Model for Understanding Protein Dynamics from Crystallographic B-Factors

Brüschweiler

2009

Biophysical Journal

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An all-atom local contact model is described that can be used to predict protein motions underlying isotropic crystallographic B-factors. It uses a mean-field approximation to represent the motion of an atom in a harmonic potential generated by the surrounding atoms resting at their equilibrium positions. Based on a 400-ns molecular dynamics simulation of ubiquitin in explicit water, it is found that each surrounding atom stiffens the spring constant by a term that on average scales exponentially with the interatomic distance. This model combines features of the local density model by Halle and the local contact model by Zhang and Brüschweiler. When applied to a nonredundant set of 98 ultra-high resolution protein structures, an average correlation coefficient of 0.75 is obtained for all atoms. The systematic inclusion of crystal contact contributions and fraying effects is found to enhance the performance substantially. Because the computational cost of the local contact model scales linearly with the number of protein atoms, it is applicable to proteins of any size for the prediction of B-factors of both backbone and side-chain atoms. The model performs as well as or better than several other models tested, such as rigid-body motional models, the local density model, and various forms of the elastic network model. It is concluded that at the currently achievable level of accuracy, collective intramolecular motions are not essential for the interpretation of B-factors.

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Normal modes and NMR order parameters in proteins

Cited by 44 publications

References 1 publication

Accuracy and precision of NMR relaxation experiments and MD simulations for characterizing protein dynamics

Accuracy and precision of NMR relaxation experiments and MD simulations for characterizing protein dynamics

Molecular dynamics and accuracy of NMR structures: Effects of error bounds and data removal

All-Atom Contact Model for Understanding Protein Dynamics from Crystallographic B-Factors

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