Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor

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

Standard

Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor. / De Graaf, Chris; Kooistra, Albert J.; Vischer, Henry F.; Katritch, Vsevolod; Kuijer, Martien; Shiroishi, Mitsunori; Iwata, So; Shimamura, Tatsuro; Stevens, Raymond C.; De Esch, Iwan J P; Leurs, Rob.

In: Journal of Medicinal Chemistry, Vol. 54, No. 23, 08.12.2011, p. 8195-8206.

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

Harvard

De Graaf, C, Kooistra, AJ, Vischer, HF, Katritch, V, Kuijer, M, Shiroishi, M, Iwata, S, Shimamura, T, Stevens, RC, De Esch, IJP & Leurs, R 2011, 'Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor', Journal of Medicinal Chemistry, vol. 54, no. 23, pp. 8195-8206. https://doi.org/10.1021/jm2011589

APA

De Graaf, C., Kooistra, A. J., Vischer, H. F., Katritch, V., Kuijer, M., Shiroishi, M., Iwata, S., Shimamura, T., Stevens, R. C., De Esch, I. J. P., & Leurs, R. (2011). Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor. Journal of Medicinal Chemistry, 54(23), 8195-8206. https://doi.org/10.1021/jm2011589

Vancouver

De Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M et al. Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor. Journal of Medicinal Chemistry. 2011 Dec 8;54(23):8195-8206. https://doi.org/10.1021/jm2011589

Author

De Graaf, Chris ; Kooistra, Albert J. ; Vischer, Henry F. ; Katritch, Vsevolod ; Kuijer, Martien ; Shiroishi, Mitsunori ; Iwata, So ; Shimamura, Tatsuro ; Stevens, Raymond C. ; De Esch, Iwan J P ; Leurs, Rob. / Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 23. pp. 8195-8206.

Bibtex

@article{e2a751c061d24c649ed26b21b75bcfa2,
title = "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor",
abstract = "The recent crystal structure determinations of druggable class A G protein-coupled receptors (GPCRs) have opened up excellent opportunities in structure-based ligand discovery for this pharmaceutically important protein family. We have developed and validated a customized structure-based virtual fragment screening protocol against the recently determined human histamine H 1 receptor (H 1R) crystal structure. The method combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≥22 heavy atoms) H 1R ligands with an exceptionally high hit rate of 73%. Of the 26 tested fragments, 19 compounds had affinities ranging from 10 μM to 6 nM. The current study shows the potential of in silico screening against GPCR crystal structures to explore novel, fragment-like GPCR ligand space.",
author = "{De Graaf}, Chris and Kooistra, {Albert J.} and Vischer, {Henry F.} and Vsevolod Katritch and Martien Kuijer and Mitsunori Shiroishi and So Iwata and Tatsuro Shimamura and Stevens, {Raymond C.} and {De Esch}, {Iwan J P} and Rob Leurs",
year = "2011",
month = dec,
day = "8",
doi = "10.1021/jm2011589",
language = "English",
volume = "54",
pages = "8195--8206",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Crystal structure-based virtual screening for fragment-like ligands of the human histamine H 1 receptor

AU - De Graaf, Chris

AU - Kooistra, Albert J.

AU - Vischer, Henry F.

AU - Katritch, Vsevolod

AU - Kuijer, Martien

AU - Shiroishi, Mitsunori

AU - Iwata, So

AU - Shimamura, Tatsuro

AU - Stevens, Raymond C.

AU - De Esch, Iwan J P

AU - Leurs, Rob

PY - 2011/12/8

Y1 - 2011/12/8

N2 - The recent crystal structure determinations of druggable class A G protein-coupled receptors (GPCRs) have opened up excellent opportunities in structure-based ligand discovery for this pharmaceutically important protein family. We have developed and validated a customized structure-based virtual fragment screening protocol against the recently determined human histamine H 1 receptor (H 1R) crystal structure. The method combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≥22 heavy atoms) H 1R ligands with an exceptionally high hit rate of 73%. Of the 26 tested fragments, 19 compounds had affinities ranging from 10 μM to 6 nM. The current study shows the potential of in silico screening against GPCR crystal structures to explore novel, fragment-like GPCR ligand space.

AB - The recent crystal structure determinations of druggable class A G protein-coupled receptors (GPCRs) have opened up excellent opportunities in structure-based ligand discovery for this pharmaceutically important protein family. We have developed and validated a customized structure-based virtual fragment screening protocol against the recently determined human histamine H 1 receptor (H 1R) crystal structure. The method combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≥22 heavy atoms) H 1R ligands with an exceptionally high hit rate of 73%. Of the 26 tested fragments, 19 compounds had affinities ranging from 10 μM to 6 nM. The current study shows the potential of in silico screening against GPCR crystal structures to explore novel, fragment-like GPCR ligand space.

UR - http://www.scopus.com/inward/record.url?scp=82555187387&partnerID=8YFLogxK

U2 - 10.1021/jm2011589

DO - 10.1021/jm2011589

M3 - Journal article

C2 - 22007643

AN - SCOPUS:82555187387

VL - 54

SP - 8195

EP - 8206

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 199377144