Co- crystallized ligand is shown in cyan when the re- docked ligand is Co- crystallized ligand is shown in cyan though the re- docked ligand is shown in purple. electronegativity favors the powerful interactions of ligand with all the proteins which can be also evident together with the binding affinity of Dactinomycin, Temsirolimus, and Everolimus. These drugs are [ https:// www. medchemexpress. com/ Abrocitinib.html Abrocitinib In Vivo] displaying highest binding affinity for NMDA, ERK, PKA, and AMPA. Although in the neutral binding pocket of CaMKII, Irrinoteacn and Bromocriptine obtaining the higher binding affinity.Plif evaluation.The protein ligand interaction fingerprints have been calculated using MOE. Dactinomycin, Temsirolimus and Everolimus are the drugs that happen to be displaying maximum affinity for NMDA, AMPA, PKA and ERK, therefore the PLIF evaluation have been performed for each of the three drugs as a way to uncover any common functional group in all of the compounds. On the basis of PLIF evaluation it can be revealed that resulting from massive molecular structure of Dactinomycin, it has many interacting points using the active website residues of NMDA, AMPA, PKA, and ERK. It might involve in H- bonding because of the presence of carboxyl group too as in hydrophobic interactions due to the presence of benzene ring (Fig. S7). Temsirolimus may also involve in H- bonding as a result of presence of terminal hydroxyl group as well as in hydrophobic interactions together with the support of extended alkane chain using the active website residues of NMDA, PKA, AMPA, and ERK (Fig. S8). Everolimus is involve in H-bonding together with the assistance of its hydroxyl and carboxyl group whilst its pyrimidine ring involved in hydrophobic interactions with NMDA, PKA and ERK (Fig. S9).The neurons of central and peripheral nervous technique as well as oligodendrocytes are specifically susceptible to off target side effects pitched in by chemotherapy30, 84. These off target effects may possibly contemplate into revamping functions of both dividing and non- dividing cells each at central and peripheral levels. The proposed mechanisms place forwarded to clarify these pathologies include faulty DNA repair mechanisms, blood brain barrier dysfunction, disordered immune regulation and impaired neurotransmitter signaling85. There is certainly an increasing proof that CICI disrupts neurogenesis particularly in adult hippocampus14,16. The implication of such reformation results in alteration of hippocampal neural circuitry which critically affects not just memory formation and finding out acquisition, but in addition interregional articulation of anatomically distant but functionally cognate brain regions86. This can be further inferred from the reported clinical proof of frontal cortical deficits by chemobrain87. For that reason, synaptic plasticity functions mediated by neurons of hippocampus are at stake. The focus from the study should be to investigate the interactions of many chemotherapeutic drugs against significant proteins involved in LTP pathway, by docking algorithm as their interacting residues could offer valuable insight into functional alteration which is often associated with cognitive processes. The outcomes derived from this study revealed that Dactinomycin, Temsirolimus, Everolimus, Docetaxel and Teniposide are major five drugs interacting with NMDA residues positioned in Ligand Binding Domain ( LBD) of GluN2 close to Glutamate binding pocket ( Fig. 7) . Contextually, NMDARs have been concentrate of pharmacological modulation by virtue of allosteric modulators, on the other hand, restricted by excessive off- target effects in lieu of excessive NMDAR inhibition.