From three-dimensional GPCR structure to rational ligand discovery

Albert J. Kooistra, Rob Leurs, Iwan J.P. De Esch, Chris De Graaf*

*Corresponding author af dette arbejde
31 Citationer (Scopus)

Abstract

This chapter will focus on G protein-coupled receptor structure-based virtual screening and ligand design. A generic virtual screening workflow and its individual elements will be introduced, covering amongst others the use of experimental data to steer the virtual screening process, ligand binding mode prediction, virtual screening for novel ligands, and rational structure-based virtual screening hit optimization. An overview of recent successful structure-based ligand discovery and design studies shows that receptor models, despite structural inaccuracies, can be efficiently used to find novel ligands for GPCRs. Moreover, the recently solved GPCR crystal structures have further increased the opportunities in structure-based ligand discovery for this pharmaceutically important protein family. The current chapter will discuss several challenges in rational ligand discovery based on GPCR structures including: (i) structure-based identification of ligands with specific effects on GPCR mediated signaling pathways, and (ii) virtual screening and structure-based optimization of fragment-like molecules.

OriginalsprogEngelsk
TitelG Protein-Coupled Receptors - Modeling and Simulation
Antal sider29
ForlagSpringer New York LLC
Publikationsdato1 jan. 2014
Sider129-157
ISBN (Trykt)9789400774223
DOI
StatusUdgivet - 1 jan. 2014
Udgivet eksterntJa
NavnAdvances in Experimental Medicine and Biology
Vol/bind796
ISSN0065-2598

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