G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

Research output: Contribution to journalJournal articleResearchpeer-review

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G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. / Ísberg, Vignir; Balle, Thomas; Sander, Tommy; Jørgensen, Flemming Steen; Gloriam, David Erik Immanuel.

In: Journal of Chemical Information and Modeling, Vol. 51, No. 2, 28.02.2011, p. 315-325.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ísberg, V, Balle, T, Sander, T, Jørgensen, FS & Gloriam, DEI 2011, 'G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations', Journal of Chemical Information and Modeling, vol. 51, no. 2, pp. 315-325. https://doi.org/10.1021/ci100402f

APA

Ísberg, V., Balle, T., Sander, T., Jørgensen, F. S., & Gloriam, D. E. I. (2011). G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. Journal of Chemical Information and Modeling, 51(2), 315-325. https://doi.org/10.1021/ci100402f

Vancouver

Ísberg V, Balle T, Sander T, Jørgensen FS, Gloriam DEI. G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. Journal of Chemical Information and Modeling. 2011 Feb 28;51(2):315-325. https://doi.org/10.1021/ci100402f

Author

Ísberg, Vignir ; Balle, Thomas ; Sander, Tommy ; Jørgensen, Flemming Steen ; Gloriam, David Erik Immanuel. / G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations. In: Journal of Chemical Information and Modeling. 2011 ; Vol. 51, No. 2. pp. 315-325.

Bibtex

@article{12f9037bacca430ebe1b820cbf56e848,
title = "G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations",
abstract = "A 5-HT(2A) receptor model was constructed by homology modeling based on the {\ss}(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability of the activated receptor model as well as revealed new information about stabilizing residues and bonds. The active 5-HT(2A) receptor model was further validated by retrospective ligand screening of more than 9400 compounds, whereof 182 were known ligands. The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Vignir {\'I}sberg and Thomas Balle and Tommy Sander and J{\o}rgensen, {Flemming Steen} and Gloriam, {David Erik Immanuel}",
year = "2011",
month = "2",
day = "28",
doi = "10.1021/ci100402f",
language = "English",
volume = "51",
pages = "315--325",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

AU - Ísberg, Vignir

AU - Balle, Thomas

AU - Sander, Tommy

AU - Jørgensen, Flemming Steen

AU - Gloriam, David Erik Immanuel

PY - 2011/2/28

Y1 - 2011/2/28

N2 - A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability of the activated receptor model as well as revealed new information about stabilizing residues and bonds. The active 5-HT(2A) receptor model was further validated by retrospective ligand screening of more than 9400 compounds, whereof 182 were known ligands. The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies.

AB - A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability of the activated receptor model as well as revealed new information about stabilizing residues and bonds. The active 5-HT(2A) receptor model was further validated by retrospective ligand screening of more than 9400 compounds, whereof 182 were known ligands. The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/ci100402f

DO - 10.1021/ci100402f

M3 - Journal article

C2 - 21261291

VL - 51

SP - 315

EP - 325

JO - Journal of Chemical Information and Modeling

JF - Journal of Chemical Information and Modeling

SN - 1549-9596

IS - 2

ER -

ID: 33097003