Molecular dynamic simulation of mGluR5 amino terminal domain: essential dynamics analysis captures the agonist or antagonist behaviour of ligands

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.

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► Molecular dynamics has been conducted for 3 agonists and 3 antagonists of mGluR5.
► Essential dynamics capture the agonist-induced or antagonist-blocked LBD responses.
► The ratio between first and second eigenvalues (R1,2) is evaluated for complexes.
► R1,2is proposed as a descriptor to discriminate mGluR5 agonists and antagonists.