In silico study of local anesthetics analogues on sodium channel Nav 1.7 a pharmacological target on inflamed dental pulp

Abstract

The Nav1.7 sodium channel are expressed in dental pulp, so identifying analogous molecules of local anesthetics with high affinity for this channel under inflammatory conditions would be very useful in dental anesthesia. The aim of this study was to evaluate local anesthetics analogues against Nav1.7 channel through molecular docking and dynamics. 3267 ligands were selected for virtual screening: 1 control ligand (Flecainide), 10 local anesthetics and 3256 structural analogues with human Nav1.7 (PDB 5EK0). Molecular protocol validation was performed with Flecainide-NavAb complex (PDB 6MVX). Molecular docking through AutoDock-Vina by binding energy between ligand-receptor and molecular dynamics simulation through AMBER16 software was developed. A predictive search of the ADME and toxicological properties were performed. The molecule-1 ligand presented the best binding energy (−6.4 kcal/mol), followed by the molecule-2 ligand with −6.3 kcal/mol. On molecular dynamics, molecule-1 analogue had the best behavior with the lowest RMSD, RMSF, SASA and Rg scores. In ADME and toxicological properties, all molecules had no violations of Lipinski's rules and had oral toxicity class III. Molecule-1 analogue can act as a potential drug for local anesthetics under inflammatory conditions by blocking pain pathways through Nav1.7 channel.

Keywords

• Anesthetics local
• Sodium channels
• Molecular docking simulation
• Molecular dynamics simulation
• Dental pulp