This was followed by ranking of the lowest energy protein-ligand interaction poses. The complexes with most adverse IFD scores have been deemed carrying favorable binding. The validation step of docking protocol was performed through re-docking from the exact same default ligand with RMSD calculations. Following re-docking, the RMSD value of co-crystallized and re-docked ligand was calculated. After the validation of docking protocol by way of re-docking, the library of chemotherapeutic compounds were docked in to the binding domains of NMDA, AMPA, PKA, CBP, CaMKII, and ERK applying the exact same protocol. The protocol generated 30 conformational poses for each drug with all selected proteins. The poses were re-scored by using GBVIWSA Dg scoring function. Binding affinity evaluation. The scoring evaluation of every single protein using the studied drugs was performed usingbox-plot function in R-3.3.3 package. Around the basis of docking scores, top five complexes for every protein with studied drugs had been selected for interaction analysis. The interaction analysis was performed working with protein ligandScientific RepoRts |(2019) 9:9630 | https:doi.org10.1038s41598-019-45883-www.nature.comscientificreportsProtein NMDA PDB ID 5KDT Resolution ( 2.44 Structure Title Structure with the human GluN1 GluN2A LBD in complicated with GNE0723 Cryo-EM structure of GluA2 bound to antagonist ZK200775 at 6.eight Angstrom resolution Crystal structure of ERK2 in complex with (S)-N-(1-(3-chloro-4fluorophenyl)-2-hydroxyethyl)-4-(four(3-chlorophenyl)-1H-pyrazol-3-yl)1H-pyrrole-2-carboxamide Protein Kinase A in complex with an Inhibitor Crystal structure on the bromodomain of human CREBBP in complex with an isoxazolylbenzimidazole ligand Full-length human CaMKII Ligandwww.nature.comscientificreportsSpecie Homo sapiens Ref(1 R,2 R)-2-[7-[[5-chloranyl-3(trifluoromethyl)pyrazol-1-yl]methyl]-5oxidanylidene-2-(trifluoromethyl)-[1,3] thiazolo[3,2-a]pyrimidin-3-yl]cyclopropane-1carbonitrile [7-morpholin-4-yl-2,3-dioxo-6(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)yl]methylphosphonic acidAMPA5KBV6.Rattus norvegicusERK2OJJ2.(s)-n-(1-(3-chloro-4-fluorophenyl)-2hydroxyethyl)-4-(4-(3-chlorophenyl)-1h-pyrazol- Homo sapiens 3-yl)-1h-pyrrole-2-carboxamide 7-(3S,4R)-4-[(5-bromothiophen-2-yl)carbonyl] pyrrolidin-3-ylquinazolin-4(3 H)-one 5-(three,5-dimethyl-1,2-oxazol-4-yl)-1-[2(morpholin-4-yl)ethyl]-2-(2-phenylethyl)-1Hbenzimidazole 4-[(two,4-dichloro-5-methoxyphenyl)amino]-6methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy] quinoline-3-carbonitrile Homo sapiens Homo sapiensPKA CBP4UJA 4NR1.93 1.To become publishedCaMKII3SOA3.Homo sapiensTable 1. List of proteins applied in the study for docking analysis.Figure four. Box plot of docking scores generated by MOE. Y-axis represent the scores even though X-axis represent the name of proteins. NMDA (N-methyl-D-aspartate receptor), AMPA (-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor), CaMKII (Ca2calmodulin-dependent protein kinase II), PKA (protein kinase A), ERK (extracellular signal egulated kinase), and CBP (CREB-binding protein). interaction profiler (PLIP) server81 and PyMOL (PyMOL, Molecular Graphics Technique, Version 2.0 Schrodinger, LLC). To further confirm the interactions amongst docked complexes, protein ligand interaction fingerprints (PLIF) had been calculated working with PLIF algorithm AT-1002 In stock implemented in MOE79,80. PLIF summarizes the interactions like H-bonds, ionic and surface contacts around the basis of.