Fig 1: Number of ligand-protein hydrogen bonds formed between AChE and the synthesized thieno[2,3-d]pyrimidine derivatives (4, 6, 9, 11, 13) and the reference drug Donepezil during 200 ns molecular dynamics simulations. Hydrogen bonds were counted using a 3.5 Å donor-acceptor distance and 120° angle cutoff, considering only interactions between the inhibitor and protein residues (excluding solvent, water, and intra-protein H-bonds). The integer count directly correlates with inhibitory potency: Compound 4 forms the most stable H-bond network (4 H-bonds) with Tyr121, Glu199, Tyr338, and Tyr335, while Compound 13 forms no significant ligand-protein H-bonds, explaining its weak activity (IC50 = 35.47 µM).