The role of electrostatic interaction in the molecular recognition of selective agonists to metabotropic glutamate receptors.
The influence of electrostatic interactions in determining selectivity for individual subtypes of metabotropic glutamate receptors (mGluRs) is evaluated for a small set of agonists by using the program Delphi and the information thus obtained is compared with docking experiments carried out with AutoDock. The evaluation of the electrostatic component of the free energy of binding for L-Glu, L-AP4, or S-PPG to mGluR1, mGluR2, and mGluR4 subtypes allowed for the detection of subtle differences in the electronic properties of the three subtypes, differences that can account for the observed agonist selectivity.
Macchiarulo
Antonio
A
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, 06123 Perugia, Italy.
Costantino
Gabriele
G
Sbaglia
Robert
R
Aiello
Stefania
S
Meniconi
Mirco
M
Pellicciari
Roberto
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism; D011422:Propionates / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity
C114785:2-amino-4-phosphono-propinate; D009943:Organophosphorus Compounds; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; C472422:S-PPG compound; C108822:metabotropic glutamate receptor 2; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; C108823:metabotropic glutamate receptor 4