Related Experiment Videos
Insights into docking and scoring neuronal alpha4beta2 nicotinic receptor agonists using molecular dynamics
Jacopo Sgrignani1, Claudia Bonaccini, Giovanni Grazioso
1Laboratorio di Molecular Modeling, Cheminformatics and QSAR, Dipartimento di Scienze Farmaceutiche, Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi, Polo Scientifico, Università degli Studi di Firenze, Via Ugo Schiff, 6, 50019 Sesto Fiorentino (FI), Italy.
Abstract:
A combined quantum mechanical (QM)-polarized docking and molecular dynamics approach to study the binding mode and to predict the binding affinity of ligands acting at the alpha4beta2-nAChR is presented. The results obtained in this study indicate that the quantum mechanical/molecular mechanics docking protocol well describes the charge-driven interactions occurring in the binding of nicotinic agonists, and it is able to represent the polarization effects on the ligand exerted by the surrounding atoms of the receptor at the binding site. This makes it possible to properly score agonists of alpha4beta2-nAChR and to reproduce the experimental binding affinity data with good accuracy, within a mean error of 2.2 kcal/mol. Moreover, applying the QM-polarized docking to an ensemble of nAChR conformations obtained from MD simulations enabled us to accurately capture nAChR-ligand induced-fit effects.
Related Concept Videos
Cholinergic Receptors: Nicotinic
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Quantitative Aspects of Drug-Receptor Interaction
The Equilibrium Binding Constant and Binding Strength
Ligand-Gated Ion Channel Receptor: Gating Mechanism