Molecular dynamics simulation of the ligand binding domain of mGluR1 in response to agonist and antagonist binding.
The interdomain movements of the ligand binding domain (LBD) of mGluR1 in response to agonist or antagonist binding are studied by 2 ns molecular dynamics (MD) simulations. Our results indicate that MD is able to reproduce many of the experimentally determined features of the open and closed conformations of LBD. Analysis of the ligand behavior over time allows to delineate some of the molecular determinants responsible for the agonist-induced or antagonist-blocked LBD responses.
Costantino
Gabriele
G
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy. gabri@unipg.it
Macchiarulo
Antonio
A
Belenikin
Maxim
M
Pellicciari
Roberto
R
D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013816:Thermodynamics
D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1