Organophosphates (OP) are broad-spectrum pesticide (also referred as nerve agents), it inhibits the acetylcholinesterase (AChE) enzyme in the synaptic gap of the nervous system leading the accumulation of Acetylcholine and neurotoxicity. Mechanistic insight of AChE inhibition has been broadlyon model organisms. Crystal structure of OP with human AChE is rarely reported in protein data bank therefore we are forced to reply upon the information generated using model organism. In this research, we have studied inhibition of OP with human AChE using Argus lab as molecular docking tools. We screened 80OPwith human AChE using Argus lab tool. Best dock score (over all binding energy) was exhibited by Phoxim (-10.7562 kcal/mol), followed by Azinphos Ethyl (-10.4978 kcal/mol) and Fonofos (-10.4752 kcal/mol). Analyzing all OP-human AChE complex individually highlights the basic insight of the interaction of OP-human AChE. OP interacts with human AChE by H-bonding (largely contributed by Ser203 and Tyr124) and ? interactions (contributed by Trp86, Phe295, Tyr337 and Tyr341). Amino acids like Trp86, Phe295 and Tyr337 are helpful in stabilizing the OP-human AChE interaction through ?-interactions. Validation studies done by Glide docking reveals Trp86 involvement in maximum Pi-Cation interaction on anionic subsite of human AChE other than Ser203 (Catalytic site). With extra precision glide docking Phoxim Ethyl Phosphonate (PEP) tops among 80OPbased on glide docking score and interacted with Trp86, Gly121 and Ser203 whereas MM-GBSA score shows less binding affinity than heptenophos and dichlorovos. Trp86 has been found closest to the OP where as Tyr337 and Tyr341 are farthest. Phe295 mostly been noticed in intramolecular ?-? interaction which is insignificant in terms of OP-AChE interaction. Study infers the importance of Tyr124, Ser203, and Trp86 which helps to hold the OP in binding cavity; however Tyr337 and Tyr341 are at the farthest.