Molecular modeling studies of the nicotinic acetylcholine receptor (nAChR) 7: Validation and analysis of bioactive compounds

The crystallographic structure of the nAChRs α7, co-crystallized with lobeline2 (1) (Figure 1) (PDB ID: 5AFN) was used in the molecular modeling validation step and analysis of bioactive compounds from literature. For this purpose, the compounds were selected based on structural similarities with 1, including the presence of aromatic subunits and subunits with basic or positively charged nitrogen atoms, as can be observed in 1 and quinucline analog (2). Between all the scoring functions evaluated on redocking validation, ASP has shown the best results, presenting lower RMSD value = 0.5252 and the atoms position of co-crystallized ligand was exactly overlapped on redocking ligand, as observed in 3 (Figure 1). In addition, the in silico model predicted well the key interactions between residues and the molecules selected from the scientific literature. The most active compounds frequently presented interactions shown in Table 1. So, this methodology can be used in virtual screening of novel compounds, in combination of docking results from bioactive compounds from literature.