title: Structure-based molecular modeling approaches to GPCR oligomerization.
abstract: Classical structure-based drug design techniques using G-protein-coupled receptors (GPCRs) as targets focus nearly exclusively on binding at the orthosteric site of a single receptor. Dimerization and oligomerization of GPCRs, proposed almost 30 years ago, have, however, crucial relevance for drug design. Targeting these complexes selectively or designing small molecules that affect receptor-receptor interactions might provide new opportunities for novel drug discovery. In order to study the mechanisms and dynamics that rule GPCRs oligomerization, it is essential to understand the dynamic process of receptor-receptor association and to identify regions that are suitable for selective drug binding, which may be determined with experimental methods such as Förster resonance energy transfer (FRET) or Bioluminescence resonance energy transfer (BRET) and computational sequence- and structure-based approaches. The aim of this chapter is to provide a comprehensive description of the structure-based molecular modeling methods for studying GPCR dimerization, that is, protein-protein docking, molecular dynamics, normal mode analysis, and electrostatics studies.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Department of Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Kaczor
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
mesh_terms: D060807:Bioluminescence Resonance Energy Transfer Techniques; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D012984:Software; D055672:Static Electricity
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled
keywords: Electrostatics; G-protein-coupled receptors; Molecular dynamics; Normal mode analysis; Protein–protein docking