Correlation of connected transitions by two-dimensional NMR spectroscopy

Griesinger, Christian; Sørensen, Ole W.; Ernst, R. R.

doi:10.1063/1.451421

Cited by 283 publications

(170 citation statements)

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“…Although most internuclear distance constraints come from NOESY data, additional information in the form of scalar coupling constant data can be obtained from other types of NMR experiments (Griesinger et al, 1986;Montelione et al, 1989Montelione et al, , 1992Bax et al, 1992;Griesinger & Eggenberger, 1992;Biamonti et al, 1994) and used to determine conformations of polypeptide dihedral angles. Scalar coupling constants are also useful for making stereospecific resonance assignments (Giintert et al, 1989(Giintert et al, , 1991Nilges et al, 1990) and confirming secondary structural features (Pardi et al, 1984;Wiithrich, 1986).…”

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confidence: 99%

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

et al. 1996

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A new functional representation of NMR-derived distance constraints, the flexible restraint potential, has been implemented in the program CONGEN (Bruccoleri RE, Karplus M, 1987, Biopolymers 26:137-168) for molecular structure generation. In addition, flat-bottomed restraint potentials for representing dihedral angle and vicinal scalar coupling constraints have been introduced into CONGEN. An effective simulated annealing (SA) protocol that combines both weight annealing and temperature annealing is described. Calculations have been performed using ideal simulated NMR constraints, in order to evaluate the use of restrained molecular dynamics (MD) with these target functions as implemented in CONGEN. In this benchmark study, internuclear distance, dihedral angle, and vicinal coupling constant constraints were calculated from the energy-minimized X-ray crystal structure of the 46-amino acid polypeptide crambin (ICRN). Three-dimensional structures of crambin that satisfy these simulated NMR constraints were generated using restrained MD and SA. Polypeptide structures with extended backbone and side-chain conformations were used as starting conformations. Dynamical annealing calculations using extended starting conformations and assignments of initial velocities taken randomly from a Maxwellian distribution were found to adequately sample the conformational space consistent with the constraints. These calculations also show that loosened internuclear constraints can allow molecules to overcome local minima in the search for a global minimum with respect to both the NMR-derived constraints and conformational energy. This protocol and the modified version of the CONGEN program described here are shown to be reliable and robust, and are applicable generally for protein structure determination by dynamical simulated annealing using NMR data.Keywords: coupling constants; energy minimization; solution NMR structure determination It is now well established that three-dimensional structures of small proteins and oligonucleotides can be determined using a combined approach of multidimensional NMR spectroscopy and computational techniques (Wiithrich, 1986; Clore &Gronen-born, 1991. Recent advances in NMR methodology make it possible to extract a large amount of structural information, Reprint requests to: Gaetano T.

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Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

et al. 1996

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“…Spectra were acquired by using mixing times ranging from 10 to 250 ms. For total correlation spectroscopy experiments (40,41), the spin-lock power was set to 49 and mixing times to 70 ms. All other parameters were identical with those in NOESY experiments. Double-quantumfiltered COSY experiments (42) were acquired at very high digital resolution, typically with 512-1,024 increments in the F1 dimension.…”

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De novodesigned cyclic-peptide heme complexes

Rosenblatt

Wang

Suslick

2003

Proc. Natl. Acad. Sci. U.S.A.

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The structural characterization of de novo designed metalloproteins together with determination of chemical reactivity can provide a detailed understanding of the relationship between protein structure and functional properties. Toward this goal, we have prepared a series of cyclic peptides that bind to water-soluble metalloporphyrins (Fe III and Co III ). Neutral and positively charged histidine-containing peptides bind with a high affinity, whereas anionic peptides bind only weakly to the negatively charged metalloporphyrin. Additionally, it was found that the peptide becomes helical only in the presence of the metalloporphyrin. CD experiments confirm that the metalloporphyrin binds specific cyclic peptides with high affinity and with isodichroic behavior. Thermal unfolding experiments show that the complex has ''native-like'' properties. Finally, NMR spectroscopy produced well dispersed spectra and experimental restraints that provide a high-resolution solution structure of the complexed peptide.O ne approach to understanding the folding and function of proteins is to attempt their design from first principles (1-3). Such design, however, requires not only incorporation of nonpolar interactions, but also inclusion of specific hydrogen bonds, disulfide bridges, ion pairs, and metal chelation. Without these interactions, proteins form compact folding intermediates referred to as molten globules (4). Molten-globule structures are compact and possess a high degree of secondary structure, but they are also highly dynamic, with both internal and external side chains rapidly interconverting among a large family of rotamers. Analysis of protein structures, on the other hand, reveals that the interior hydrophobic core is well packed and rigid. Therefore, two challenges occur in the design of ''native-like'' proteins. By using positive design (3, 5-7), one can take into account issues such as hydrophobicity and the helix-or sheet-forming propensity of amino acids. By using negative design [a term developed to describe the selective introduction of unique stabilizing interactions (2, 3)], one can introduce features that stabilize one specific fold, while, at the same time, they destabilize alternative topologies. By using this dual strategy, one can increase the free-energy gap between the native and molten-globule states.With the challenge of design making rapid progress, several groups have begun to look at the incorporation of functional cofactors in hopes of producing de novo catalytic proteins (8-14). Many enzymes require mono-and dinuclear metal ions (15), metal clusters (ferredoxin and nitrogenase) (16), heme (cytochromes and globins) (17), and organic cofactors (flavin-and quinone-based enzymes) (18). These cofactors are important, especially when processes such as oxidation͞reduction or substrate binding and activation are required (15).Studies of natural enzymes have led to considerable understanding of their structure and function. Reduction of these complicated systems to minimal models, however, will allow ...

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“…Their multiplet fine structures are complementary in the sense that one term is antiphase with respect to J HX and the other is in-phase. As a result, half of the multiplet components are cancelled out and an E. COSY-type multiplet pattern (Griesinger et al 1986) is observed both for the diagonal peaks and the cross-peaks Montelione et al 1989). This unique fine structure makes experiments with XCwJ-half-filters attractive for measurements of small heteronuclear multiple-bond coupling constants, which are usually not resolved in the 'H-NMR spectra of macromolecules.…”

Section: ^H^-cosy and Phfhl-noesy With Xfaj-half-filtermentioning

confidence: 99%

“…For example, in NOESY [equation (5)] the diagonal peaks of X-bound protons would be represented by the superposition of the in-phase multiplet cos Qt 1 cos 7r7 H x f i H y with the antiphase multiplet -sin Qt x sin 7r7 H x*i 2^J / X Z . Only half of the multiplet components are thus observed in the standard 2D ['H^Hj-NMR spectra of X-coupled protons, and the resulting multiplet pattern is of E. COSY-type (Griesinger et al 1986) with respect to the heteronuclear coupling. (This phenomenon was initially observed and analyzed in ^H^HJ-COSY spectra of [ U3 Cd 7 ]-metallothionein (Neuhaus et al 1984)).…”

Section: Product Operator Description Of X-filters In ^H^ffi-cosy Andmentioning

confidence: 99%

Heteronuclear filters in two-dimensional [¹H, ¹H]-NMR spectroscopy: combined use with isotope labelling for studies of macromolecular conformation and intermolecular interactions

Otting¹,

Wüthrich²

1990

Quart. Rev. Biophys.

355

184

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The use of heteronuclear filters enables the editing of complex 1H nuclear magnetic resonance (NMR) spectra into simplified subspectra containing a lesser number of resonance lines, which are then more easily amenable to detailed spectral analysis. This editing is based on the creation of heteronuclear two-spin or multiple-spin coherence and discrimination between protons that do or do not participate in these heteronuclear coherences. In principle, heteronuclear editing can be used in conjunction with one-dimensional or multidimensional 1H-NMR experiments for studies of a wide variety of low-molecular-weight compounds or macromolecular systems, and is implicitely applied in a wide range of heteronuclear NMR experiments with proton detection (e.g. Bax et al. 1983; Griffey & Redfield, 1987). In the present article we shall focus on the use of heteronuclear filters in two-dimensional (2D) [1H, 1H]-NMR experiments. The selection of the material covered was primarily motivated by its impact on the practice of protein structure determination in solution, and on NMR studies of intermolecular interactions with biological macromolecules. Section 2 surveys potential applications of heteronuclear filters in this area. The remainder of the article is devoted to an introduction of the theoretical principles used in heteronuclear filters, and to a detailed description of the experimental implementation of these measurements. In writing the review we tried to minimize redundancy with the recent article in Quarterly Review of Biophysics by Griffey & Redfield (1987) and to concentrate on experiments that were introduced during the period 1986–9.

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Correlation of connected transitions by two-dimensional NMR spectroscopy

Cited by 283 publications

References 26 publications

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

De novodesigned cyclic-peptide heme complexes

Heteronuclear filters in two-dimensional [¹H, ¹H]-NMR spectroscopy: combined use with isotope labelling for studies of macromolecular conformation and intermolecular interactions

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Correlation of connected transitions by two-dimensional NMR spectroscopy

Cited by 283 publications

References 26 publications

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

De novodesigned cyclic-peptide heme complexes

Heteronuclear filters in two-dimensional [1H, 1H]-NMR spectroscopy: combined use with isotope labelling for studies of macromolecular conformation and intermolecular interactions

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Heteronuclear filters in two-dimensional [¹H, ¹H]-NMR spectroscopy: combined use with isotope labelling for studies of macromolecular conformation and intermolecular interactions