Mapping histamine H4 receptor-ligand binding modes

Research output: Contribution to journal › Journal article › Research › peer-review

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Mapping histamine H4 receptor-ligand binding modes. / Schultes, Sabine; Nijmeijer, Saskia; Engelhardt, Harald; Kooistra, Albert J.; Vischer, Henry F.; De Esch, Iwan J P; Haaksma, Eric E J; Leurs, Rob; De Graaf, Chris.

In: MedChemComm, Vol. 4, No. 1, 01.01.2013, p. 193-204.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schultes, S, Nijmeijer, S, Engelhardt, H, Kooistra, AJ, Vischer, HF, De Esch, IJP, Haaksma, EEJ, Leurs, R & De Graaf, C 2013, 'Mapping histamine H4 receptor-ligand binding modes', MedChemComm, vol. 4, no. 1, pp. 193-204. https://doi.org/10.1039/c2md20212c

APA

Schultes, S., Nijmeijer, S., Engelhardt, H., Kooistra, A. J., Vischer, H. F., De Esch, I. J. P., Haaksma, E. E. J., Leurs, R., & De Graaf, C. (2013). Mapping histamine H4 receptor-ligand binding modes. MedChemComm, 4(1), 193-204. https://doi.org/10.1039/c2md20212c

Vancouver

Schultes S, Nijmeijer S, Engelhardt H, Kooistra AJ, Vischer HF, De Esch IJP et al. Mapping histamine H4 receptor-ligand binding modes. MedChemComm. 2013 Jan 1;4(1):193-204. https://doi.org/10.1039/c2md20212c

Author

Schultes, Sabine ; Nijmeijer, Saskia ; Engelhardt, Harald ; Kooistra, Albert J. ; Vischer, Henry F. ; De Esch, Iwan J P ; Haaksma, Eric E J ; Leurs, Rob ; De Graaf, Chris. / Mapping histamine H4 receptor-ligand binding modes. In: MedChemComm. 2013 ; Vol. 4, No. 1. pp. 193-204.

Bibtex

@article{ef9e289335cb4ab8ac679b74d78b0826,
title = "Mapping histamine H4 receptor-ligand binding modes",
abstract = "The increasing number of G protein-coupled receptor (GPCR) crystal structures offers new opportunities for histamine receptor homology modeling. However, computational prediction of ligand binding modes in GPCRs such as the histamine H4 receptor (H4R), a receptor that plays an important role in inflammation, remains a challenging task. In the current work we have combined complementary in silico receptor modeling approaches with in vitro ligand structure-activity relationship (SAR) and protein site-directed mutagenesis studies to elucidate the binding modes of different ligand classes in H4R. By systematically considering different H4R modelling templates, ligand binding poses, and ligand protonation states in combination with docking and MD simulations we are able to explain ligand-specific mutation effects and subtle differences in ligand SAR. Our studies confirm that a combined theoretical and experimental approach represents a powerful strategy to map ligand-protein interactions.",
author = "Sabine Schultes and Saskia Nijmeijer and Harald Engelhardt and Kooistra, {Albert J.} and Vischer, {Henry F.} and {De Esch}, {Iwan J P} and Haaksma, {Eric E J} and Rob Leurs and {De Graaf}, Chris",
year = "2013",
month = jan,
day = "1",
doi = "10.1039/c2md20212c",
language = "English",
volume = "4",
pages = "193--204",
journal = "MedChemComm",
issn = "2040-2503",
publisher = "Royal Society of Chemistry",
number = "1",

}

RIS

TY - JOUR

T1 - Mapping histamine H4 receptor-ligand binding modes

AU - Schultes, Sabine

AU - Nijmeijer, Saskia

AU - Engelhardt, Harald

AU - Kooistra, Albert J.

AU - Vischer, Henry F.

AU - De Esch, Iwan J P

AU - Haaksma, Eric E J

AU - Leurs, Rob

AU - De Graaf, Chris

PY - 2013/1/1

Y1 - 2013/1/1

N2 - The increasing number of G protein-coupled receptor (GPCR) crystal structures offers new opportunities for histamine receptor homology modeling. However, computational prediction of ligand binding modes in GPCRs such as the histamine H4 receptor (H4R), a receptor that plays an important role in inflammation, remains a challenging task. In the current work we have combined complementary in silico receptor modeling approaches with in vitro ligand structure-activity relationship (SAR) and protein site-directed mutagenesis studies to elucidate the binding modes of different ligand classes in H4R. By systematically considering different H4R modelling templates, ligand binding poses, and ligand protonation states in combination with docking and MD simulations we are able to explain ligand-specific mutation effects and subtle differences in ligand SAR. Our studies confirm that a combined theoretical and experimental approach represents a powerful strategy to map ligand-protein interactions.

AB - The increasing number of G protein-coupled receptor (GPCR) crystal structures offers new opportunities for histamine receptor homology modeling. However, computational prediction of ligand binding modes in GPCRs such as the histamine H4 receptor (H4R), a receptor that plays an important role in inflammation, remains a challenging task. In the current work we have combined complementary in silico receptor modeling approaches with in vitro ligand structure-activity relationship (SAR) and protein site-directed mutagenesis studies to elucidate the binding modes of different ligand classes in H4R. By systematically considering different H4R modelling templates, ligand binding poses, and ligand protonation states in combination with docking and MD simulations we are able to explain ligand-specific mutation effects and subtle differences in ligand SAR. Our studies confirm that a combined theoretical and experimental approach represents a powerful strategy to map ligand-protein interactions.

UR - http://www.scopus.com/inward/record.url?scp=84871799204&partnerID=8YFLogxK

U2 - 10.1039/c2md20212c

DO - 10.1039/c2md20212c

M3 - Journal article

VL - 4

SP - 193

EP - 204

JO - MedChemComm

JF - MedChemComm

SN - 2040-2503

IS - 1

ER -

ID: 199376791