title: Computer-aided design of GPCR ligands.
abstract: The recent availability of several GPCR crystal structures now contributes decisively to the perspective of structure-based ligand design. In this context, computational approaches are extremely helpful, particularly if properly integrated in drug design projects with cooperation between computational and medicinal chemistry teams. Here, we present the pipelines used in one such project, devoted to the design of novel potent and selective antagonists for the different adenosine receptors. The details of the computational strategies are described, and particular attention is given to explain how these procedures can effectively guide the synthesis of novel chemical entities.
authors.affiliation: Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, SE-751 24, Uppsala, Sweden, hugo.gutierrez@icm.uu.se.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gutiérrez-de-Terán
authors.forename: Henrik
authors.initials: H
authors.lastname: Keränen
authors.forename: Jhonny
authors.initials: J
authors.lastname: Azuaje
authors.forename: David
authors.initials: D
authors.lastname: Rodríguez
authors.forename: Johan
authors.initials: J
authors.lastname: Åqvist
authors.forename: Eddy
authors.initials: E
authors.lastname: Sotelo
mesh_terms: D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D017076:Computer-Aided Design; D015195:Drug Design; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D018047:Receptors, Purinergic P1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D008024:Ligands; D020033:Protein Isoforms; D018047:Receptors, Purinergic P1; D054852:Small Molecule Libraries