Homology Modeling of Dopamine D2 and D3 Receptors: Molecular Dynamics Refinement and Docking Evaluation
Chiara Bianca Maria Platania,Salvatore Salomone,Gian Marco Leggio,Filippo Drago,Claudio Bucolo +4 more
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TLDR
The present computational approach seems suitable to build and refine structure models of homologous dopamine receptors that may be of value for structure-based drug discovery of selective dopaminergic ligands.Abstract:
Dopamine (DA) receptors, a class of G-protein coupled receptors (GPCRs), have been targeted for drug development for the treatment of neurological, psychiatric and ocular disorders. The lack of structural information about GPCRs and their ligand complexes has prompted the development of homology models of these proteins aimed at structure-based drug design. Crystal structure of human dopamine D3 (hD3) receptor has been recently solved. Based on the hD3 receptor crystal structure we generated dopamine D2 and D3 receptor models and refined them with molecular dynamics (MD) protocol. Refined structures, obtained from the MD simulations in membrane environment, were subsequently used in molecular docking studies in order to investigate potential sites of interaction. The structure of hD3 and hD2L receptors was differentiated by means of MD simulations and D3 selective ligands were discriminated, in terms of binding energy, by docking calculation. Robust correlation of computed and experimental Ki was obtained for hD3 and hD2L receptor ligands. In conclusion, the present computational approach seems suitable to build and refine structure models of homologous dopamine receptors that may be of value for structure-based drug discovery of selective dopaminergic ligands.read more
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Dopamine D(3) receptor as a new pharmacological target for the treatment of depression.
Gian Marco Leggio,Salvatore Salomone,Claudio Bucolo,Chiara Bianca Maria Platania,Vincenzo Micale,Filippo Caraci,Filippo Drago +6 more
TL;DR: Dopamine D3 receptor expression and function are both down-regulated in stress and depression, and these changes are reversed by antidepressant treatments, suggesting that enhanced dopaminergic neurotransmission mediated by dopamine D3 receptors participates in adaptive changes related to antidepressant activity.
Journal ArticleDOI
Current drug treatments targeting dopamine D3 receptor.
Gian Marco Leggio,Claudio Bucolo,Chiara Bianca Maria Platania,Salvatore Salomone,Filippo Drago +4 more
TL;DR: An overview of studies indicating D3R as a target for pharmacological therapy, and a review of market approved drugs endowed with significant affinity at D2-like receptor subtype that are used to treat disorders where D 3R plays a relevant role are provided.
Journal ArticleDOI
Pharmacological management of ocular hypertension: current approaches and future prospective
Claudio Bucolo,Salvatore Salomone,Filippo Drago,Michele Reibaldi,Antonio Longo,Maurizio G. Uva +5 more
TL;DR: This review focuses on pharmacological management of ocular hypertension with a particular attention to the future pharmacotherapy scenario.
Journal ArticleDOI
Dopamine outside the brain: The eye, cardiovascular system and endocrine pancreas.
TL;DR: Data is summarized on DA and DRs in the eye, cardiovascular system and endocrine pancreas, three districts where DA and DA-related drugs have been studied and the expression of DR documented, to enable a full comprehension of peripheral DA signaling.
Journal ArticleDOI
N, N′-Olefin Functionalized Bis-Imidazolium Gold(I) Salt Is an Efficient Candidate to Control Keratitis-Associated Eye Infection
Tapastaru Samanta,Gourisankar Roymahapatra,William F. Porto,Saikat Kumar Seth,Sudipta Ghorai,Suman Saha,Jayangshu Sengupta,Octavio L. Franco,Joydev Dinda,Santi M. Mandal +9 more
TL;DR: The new precursor, 3,3′-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide and its analogous PF6 salt were synthesized and suggest that its target is the cell membrane.
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