Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain

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

Standard

Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain. / Akdemir, Atilla; Edink, Ewald; Thompson, Andrew J.; Lummis, Sarah C.R.; Kooistra, Albert J.; De Graaf, Chris; De Esch, Iwan J.P.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 19, 01.10.2012, p. 5992-6002.

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

Harvard

Akdemir, A, Edink, E, Thompson, AJ, Lummis, SCR, Kooistra, AJ, De Graaf, C & De Esch, IJP 2012, 'Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain', Bioorganic and Medicinal Chemistry, vol. 20, no. 19, pp. 5992-6002. https://doi.org/10.1016/j.bmc.2012.06.054

APA

Akdemir, A., Edink, E., Thompson, A. J., Lummis, S. C. R., Kooistra, A. J., De Graaf, C., & De Esch, I. J. P. (2012). Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain. Bioorganic and Medicinal Chemistry, 20(19), 5992-6002. https://doi.org/10.1016/j.bmc.2012.06.054

Vancouver

Akdemir A, Edink E, Thompson AJ, Lummis SCR, Kooistra AJ, De Graaf C et al. Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain. Bioorganic and Medicinal Chemistry. 2012 Oct 1;20(19):5992-6002. https://doi.org/10.1016/j.bmc.2012.06.054

Author

Akdemir, Atilla ; Edink, Ewald ; Thompson, Andrew J. ; Lummis, Sarah C.R. ; Kooistra, Albert J. ; De Graaf, Chris ; De Esch, Iwan J.P. / Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 19. pp. 5992-6002.

Bibtex

@article{618d6ebafded4f33aa8e7625e3ca5968,
title = "Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain",
abstract = "A hierarchical in silico screening procedure using the crystal structure of an agonist bound chimeric α7/Ls-AChBP protein was successfully applied to both proprietary and commercial databases containing drug-like molecules. An overall hit rate of 26% (pKi ≥5.0) was obtained, with an even better hit rate of 35% for the commercial compound collection. Structurally novel and diverse ligands were identified. Binding studies with [ 3H]epibatidine on chimeric α7/5-HT3 receptors yielded submicromolar inhibition constants for identified hits. Compared to a previous screening procedure that utilized the wild type Ls-AChBP crystal structure, the current study shows that the recently obtained α7/Ls-AChBP chimeric protein crystal structure is a better template for the identification of novel α7 receptor ligands.",
keywords = "α7 Receptor, AChBP, Cys-loop, Docking, In silico screening, nAChR, Virtual screening",
author = "Atilla Akdemir and Ewald Edink and Thompson, {Andrew J.} and Lummis, {Sarah C.R.} and Kooistra, {Albert J.} and {De Graaf}, Chris and {De Esch}, {Iwan J.P.}",
year = "2012",
month = oct,
day = "1",
doi = "10.1016/j.bmc.2012.06.054",
language = "English",
volume = "20",
pages = "5992--6002",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "19",

}

RIS

TY - JOUR

T1 - Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain

AU - Akdemir, Atilla

AU - Edink, Ewald

AU - Thompson, Andrew J.

AU - Lummis, Sarah C.R.

AU - Kooistra, Albert J.

AU - De Graaf, Chris

AU - De Esch, Iwan J.P.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - A hierarchical in silico screening procedure using the crystal structure of an agonist bound chimeric α7/Ls-AChBP protein was successfully applied to both proprietary and commercial databases containing drug-like molecules. An overall hit rate of 26% (pKi ≥5.0) was obtained, with an even better hit rate of 35% for the commercial compound collection. Structurally novel and diverse ligands were identified. Binding studies with [ 3H]epibatidine on chimeric α7/5-HT3 receptors yielded submicromolar inhibition constants for identified hits. Compared to a previous screening procedure that utilized the wild type Ls-AChBP crystal structure, the current study shows that the recently obtained α7/Ls-AChBP chimeric protein crystal structure is a better template for the identification of novel α7 receptor ligands.

AB - A hierarchical in silico screening procedure using the crystal structure of an agonist bound chimeric α7/Ls-AChBP protein was successfully applied to both proprietary and commercial databases containing drug-like molecules. An overall hit rate of 26% (pKi ≥5.0) was obtained, with an even better hit rate of 35% for the commercial compound collection. Structurally novel and diverse ligands were identified. Binding studies with [ 3H]epibatidine on chimeric α7/5-HT3 receptors yielded submicromolar inhibition constants for identified hits. Compared to a previous screening procedure that utilized the wild type Ls-AChBP crystal structure, the current study shows that the recently obtained α7/Ls-AChBP chimeric protein crystal structure is a better template for the identification of novel α7 receptor ligands.

KW - α7 Receptor

KW - AChBP

KW - Cys-loop

KW - Docking

KW - In silico screening

KW - nAChR

KW - Virtual screening

UR - http://www.scopus.com/inward/record.url?scp=84866434365&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2012.06.054

DO - 10.1016/j.bmc.2012.06.054

M3 - Journal article

C2 - 22959526

AN - SCOPUS:84866434365

VL - 20

SP - 5992

EP - 6002

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 19

ER -

ID: 199376408