title: Molecular dynamic simulation of mGluR5 amino terminal domain: essential dynamics analysis captures the agonist or antagonist behaviour of ligands.
abstract: We describe the application of molecular dynamics followed by principal component analysis to study the inter-domain movements of the ligand binding domain (LBD) of mGluR5 in response to the binding of selected agonists or antagonists. Our results suggest that the method is an attractive alternative to current approaches to predict the agonist-induced or antagonist-blocked LBD responses. The ratio between the eigenvalues of the first and second eigenvectors (R1,2) is also proposed as a numerical descriptor for discriminating the ligand behavior as a mGluR5 agonist or antagonist.
authors.affiliation: Dipartimento di Scienze Farmaceutiche - sezione di Chimica Generale e Organica Alessandro Marchesini, Università degli Studi di Milano, via Venezian, 21 20133 Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Casoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.forename: Alessandro
authors.initials: A
authors.lastname: Contini
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001665:Binding Sites; D018698:Glutamic Acid / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D010648:Phenylacetates / Q000737:chemistry*; D025341:Principal Component Analysis; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016318:Quisqualic Acid / Q000737:chemistry*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D014966:Xanthenes / Q000737:chemistry*
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D000596:Amino Acids; C578935:GRM5 protein, human; D008024:Ligands; D010648:Phenylacetates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C474696:methyl-(4-carboxyphenyl)glycine; D018698:Glutamic Acid; D016318:Quisqualic Acid; C420102:LY 344545; D005998:Glycine