The binding site locations and structural components for type I and type II positive allosteric modulators (PAMs) of the α7 nicotinic acetylcholine receptor (nAChR) have not been fully characterized yet. In this regard, homology models of the human α7 nAChR and hα7/m5-HT chimera, built using the crystal structure of the serotonin type 3A receptor (5-ΗΤR), were used for molecular docking and molecular dynamics simulations to study the molecular interactions of selected type I (5-hydroxyindol, NS-1738, and LY-2087101) and type II (PNU-120596, PAM-2, and TBS-516) PAMs. The docking results indicate: (1) a site located in the extracellular domain (ECD) for type I PAMs such as NS-1738 and LY-2087101, but not for 5-HI; (2) an overlapping site in the ECD-transmembrane domain (TMD) junction for all studied PAMs. Additional docking results on the hα7/m5-HT chimera supported experimental results indicating that the ECD site might be relevant for type I PAM activity; and (3) two TMD sites, an intrasubunit site that recognizes type II PAMs, and an intersubunit pocket with high specificity for 5-HI (type I PAM). The in silico α7TSLMF mutant results support the view that M1-Ser223 and M3-Ile281 are key residues for the interaction of PAM-2 and PNU-120596 with the intrasubunit cavity. Our in silico results are in agreement with experimental data showing that the intrasubunit cavity is relevant for the activity of type II PAMs, and suggest that the ECD-TMD junction and intersubunit sites could be significant for the activity of type I PAMs.