<sup>1</sup> H nuclear magnetic resonance studies of thyrotropin releasing factor (TRF)

Feeney, J.; Bedford, G. R.; Wessels, Philippus L.

doi:10.1016/0014-5793(74)80762-3

Cited by 20 publications

(2 citation statements)

References 10 publications

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“…As can be seen in Figure 5a the values of ψ 1 cover a wide range of angles with a broad maximum around 50°and two additional smaller populations around (150°. This agrees with the proposed free rotation of this torsional angle based on NMR measurements (Feeney et al, 1974) but poses specific questions about the role of interactions between pyroGlu and Asn110. The population around 50°corresponds to structures that maintain an H-bond between the N-H of pyroGlu and the CdO group of the carboxamide of Asn110.…”

Section: Resultssupporting

confidence: 88%

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

et al. 1996

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Previous mutational and computational studies of the thyrotropin-releasing hormone (TRH) receptor identified several residues in its binding pocket [see accompanying paper, Perlman et al. (1996) Biochemistry 35, 7643-7650]. On the basis of the initial model constructed with standard energy minimization techniques, we have conducted 15 mixed mode Monte Carlo/stochastic dynamics (MC-SD) simulations to allow for extended sampling of the conformational states of the ligand and the receptor in the complex. A simulated annealing protocol was adopted in which the complex was cooled from 600 to 310 K in segments of 30 ps of the MC-SD simulations for each change of 100 K. Analysis of the simulation results demonstrated that the mixed mode MC-SD protocol maintained the desired temperature in the constant temperature simulation segments. The elevated temperature and the repeating simulations allowed for adequate sampling of the torsional space of the complex with successful conservation of the general structure and good helicity of the receptor. For the analysis of the interaction between TRH and the binding pocket, TRH was divided into four groups consisting of pyroGlu, His, ProNH2, and the backbone. The pairwise interaction energies of the four separate portions of TRH with the corresponding residues in the receptor provide a physicochemical basis for the understanding of ligand-receptor complexes. The interaction of pyroGlu with Tyr106 shows a bimodal distribution that represents two populations: one with a H-bond and another without it. Asp195 was shown to compete with pyroGlu for the H-bond to Tyr106. Simulations in which Asp195 was interacting with Arg283, thus removing it from the vicinity of Tyr106, resulted in a stable H-bond to pyroGlu. In all simulations His showed a van der Waals attraction to Tyr282 and a weak electrostatic repulsion from Arg 306. The ProNH2 had a strong and frequent H-bonding interaction with Arg306. The backbone carbonyls show a frequent H-bonding interaction with the OH group of Tyr282 and strong, often multiple, interactions with Arg306. Three structures, which maintained these interactions simultaneously, were selected as candidates for ligand-receptor complexes. These show persistent interactions of TRH with Ile 109 and Ile 116 in HX 3 and with Tyr310 and Ser313 in HX 7, which will be tested to refine the structure of the ligand-receptor complex. The superposition of the three structures shows the extent of structural flexibility of the receptor and the ligand in the complex. The backbone of TRH inside the receptor is in an alpha-helical conformation, suggesting that the receptor, through its interaction with the ligand, provides the energy required for the conformational change in the ligand from an extended to the folded form.

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Section: Resultssupporting

confidence: 88%

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

et al. 1996

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“…Conformational studies, both theoretical and experimental, are also numerous. The choices of conformation permitted by this short peptide molecule, which contains a proline residue known to introduce significant steric hindrance, are reflected in the various models proposed (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue.

Haar¹,

Fermandjian²,

Vičar³

et al. 1975

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

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Conformational studies on the hypothalamic thyrotropin releasing factor and related compounds by ¹H nuclear magnetic resonance spectroscopy

1974

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synopsisProton magnetic resonance studies a t 220 MHz were carried out on the hypothalamic thyrotropin releasing factor (TRF) and a variety of synthetic analogs designed to yield specific information about side chain-side chain and side chain-backbone interactions. The results show that the very low field resonance position of one of the carboxamide protons observed for T R F dissolved in dimethylsulfoxide is neither caused by a sevenmembered nor by a ten-membered hydrogen bonded ring, but rather is due to a short range interaction between the unprotonated histidyl side chain and the carboxamide residue. A systematic study of the preferred histidyl side chain conformation in various T R F analogs is in good agreement with this interpretation. It was demonstrated that this interaction is not strong enough to cause significant changes in the preferred backbone conformation of the hormone. The possibilities for typical dipole-dipole interaction are discussed. No such interaction has been detected in T R F dissolved in water. We conclude that the tertiary structure of T R F in polar solvents is determined primarily by the steric characteristics of the bulky side chains which maintain the molecule preferentially in an extended conformation.

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¹ H nuclear magnetic resonance studies of thyrotropin releasing factor (TRF)

Cited by 20 publications

References 10 publications

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue.

Conformational studies on the hypothalamic thyrotropin releasing factor and related compounds by ¹H nuclear magnetic resonance spectroscopy

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1 H nuclear magnetic resonance studies of thyrotropin releasing factor (TRF)

Cited by 20 publications

References 10 publications

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

A Refined Model of the Thyrotropin-Releasing Hormone (TRH) Receptor Binding Pocket. Novel Mixed Mode Monte Carlo/Stochastic Dynamics Simulations of the Complex between TRH and TRH Receptor

13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue.

Conformational studies on the hypothalamic thyrotropin releasing factor and related compounds by 1H nuclear magnetic resonance spectroscopy

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¹ H nuclear magnetic resonance studies of thyrotropin releasing factor (TRF)

Conformational studies on the hypothalamic thyrotropin releasing factor and related compounds by ¹H nuclear magnetic resonance spectroscopy