Recently, researchers have used acetylcholinesterase (AChE) as a reaction vessel to synthesize its own inhibitors. Thus, 1 (syn-TZ2PA6), a femtomolar AChE inhibitor, which is formed in a 1:1 mixture with its anti-isomer by solution phase reaction from 3 (TZ2) and 4 (PA6), can be synthesized exclusively inside the AChE gorge. Our computational approach based on quantum mechanical/molecular mechanical (QM/MM) calculations, molecular dynamics (MD), and targeted molecular dynamics (TMD) studies answers why 1 is the sole product in the AChE environment. Ab initio QM/MM results show that the reaction in the AChE gorge occurs when 3/azide and 4/acetylene are extended in a parallel orientation. An MD simulation started from the final structure of QM/MM calculations keeps the azide's and acetylene's parallel orientations intact for 10 ns of simulation time. A TMD simulation applied on an antiparallel azide-acetylene conformation flips the acetylene easily to bring it to a position that is parallel to azide. A second set of QM/MM calculations performed on this flipped structure generates a similar minimum-energy path as obtained previously. Even a TMD simulation carried out on a parallel azide-acetylene conformation could not deform their parallel arrangement. All of these results, thus, imply that inside the AChE gorge, the azide group of 3 and the acetylene group of 4 always remain parallel, with the consequence that 1 is the only product. The architecture of the gorge plays an important role in this selective formation of 1.