Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model

Autoren

Benny Kneissl
Bettina Leonhardt
Andreas Hildebrandt
Christofer S Tautermann

DOI

10.1021/jm8014487

eISSN

1520-4804

ISSN

0022-2623

Ausgabe der Veröffentlichung

10

Zeitschrift

Journal of Medicinal Chemistry

Sprache

en

Online publication date

2009

Paginierung

3166 - 3173

Datum der Veröffentlichung

2009

Status

Published

Herausgeber

American Chemical Society (ACS)

Herausgeber URL

http://dx.doi.org/10.1021/jm8014487

Datum der Datenerfassung

2023

Titel

Revisiting Automated G-Protein Coupled Receptor Modeling: The Benefit of Additional Template Structures for a Neurokinin-1 Receptor Model

Ausgabe der Zeitschrift

52

Datenquelle: Crossref

Abstract

The feasibility of automated procedures for the modeling of G-protein coupled receptors (GPCR) is investigated on the example of the human neurokinin-1 (NK1) receptor. We use a combined method of homology modeling and molecular docking and analyze the information content of the resulting docking complexes regarding the binding mode for further refinements. Moreover, we explore the impact of different template structures, the bovine rhodopsin structure, the human beta(2) adrenergic receptor, and in particular a combination of both templates to include backbone flexibility in the target conformational space. Our results for NK1 modeling demonstrate that model selection from a set of decoys can in general not solely rely on docking experiments but still requires additional mutagenesis data. However, an enrichment factor of 2.6 in a nearly fully automated approach indicates that reasonable models can be created automatically if both available templates are used for model construction. Thus, the recently resolved GPCR structures open new ways to improve the model building fundamentally.

Addresses

Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany.

Autoren

Benny Kneissl
Bettina Leonhardt
Andreas Hildebrandt
Christofer S Tautermann

DOI

10.1021/jm8014487

eISSN

1520-4804

Externe Identifier

PubMed Identifier: 19397376

Open access

false

ISSN

0022-2623

Ausgabe der Veröffentlichung

10

Zeitschrift

Journal of medicinal chemistry

Schlüsselwörter

Animals
Cattle
Humans
Receptors, G-Protein-Coupled
Receptors, Neurokinin-1
Protein Binding
Models, Molecular
Automation
Computer Simulation

Sprache

eng

Medium

Print

Paginierung

3166 - 3173

Datum der Veröffentlichung

2009

Status

Published

Datum der Datenerfassung

2009

Titel

Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

52

Datenquelle: Europe PubMed Central

Abstract

The feasibility of automated procedures for the modeling of G-protein coupled receptors (GPCR) is investigated on the example of the human neurokinin-1 (NK1) receptor. We use a combined method of homology modeling and molecular docking and analyze the information content of the resulting docking complexes regarding the binding mode for further refinements. Moreover, we explore the impact of different template structures, the bovine rhodopsin structure, the human beta(2) adrenergic receptor, and in particular a combination of both templates to include backbone flexibility in the target conformational space. Our results for NK1 modeling demonstrate that model selection from a set of decoys can in general not solely rely on docking experiments but still requires additional mutagenesis data. However, an enrichment factor of 2.6 in a nearly fully automated approach indicates that reasonable models can be created automatically if both available templates are used for model construction. Thus, the recently resolved GPCR structures open new ways to improve the model building fundamentally.

Autoren

Benny Kneissl
Bettina Leonhardt
Andreas Hildebrandt
Christofer S Tautermann

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/19397376

DOI

10.1021/jm8014487

eISSN

1520-4804

Ausgabe der Veröffentlichung

10

Zeitschrift

J Med Chem

Schlüsselwörter

Animals
Automation
Cattle
Computer Simulation
Humans
Models, Molecular
Protein Binding
Receptors, G-Protein-Coupled
Receptors, Neurokinin-1

Sprache

eng

Country

United States

Paginierung

3166 - 3173

Datum der Veröffentlichung

2009

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2009

Titel

Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

52

Datenquelle: PubMed

Autoren

Benny Kneissl
Bettina Leonhardt
Andreas Hildebrandt
Christofer S Tautermann

Zeitschrift

Journal of medicinal chemistry

Artikelnummer

10

Paginierung

3166 - 3173

Datum der Veröffentlichung

2009

Herausgeber

ACS Publications

Datum der Datenerfassung

2020

Titel

Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model

Sub types

article

Ausgabe der Zeitschrift

52

Datenquelle: Manual

Revisiting automated G-protein coupled receptor modeling: the benefit of additional template structures for a neurokinin-1 receptor model

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