Docking of various molecules including two NSAIDs as prototypes into the COX-1 enzyme
Keywords:
COX-1, Docking, NSAIDs, Ketoprofen, Ibuprofen. Abstract
Molecular modeling studies for the cyclo-oxygenase isozyme (COX-1) and docking processes in the COX-1 active site pocket is of an importance of research in Today’s world. This is preformed in order to study the inhibition effect of these different compounds to the COX-1 enzyme by using molecular operation environment (MOE) program. Teen different chemical molecules were fitted in the active site pocket of the COX-1 enzyme and optimized in both cases before and after molecular dynamic simulations that is after taking the best conformation of each ligand of these molecules depending upon scoring investigation. The energy gain for the whole system is obtained by the subtraction of the complexed systems energies from the separated ones. The teen neutral (protonated) molecules were studied and show that the compound 3, 7 and 9 under re-optimization process after MD simulation show the best fitting among all studied molecules and their energy gains were -34.2, -40.4 and -41.21 kcal/mol, respectively. In order to know the effect of ionization on the system, The possible ionized compounds 1, 2 and 3 were studied in both the neutral and deprotonated forms. The obtained results show that both compound 1 and 2 show relatively small inhibition once they studied as in their neutral species. The effect of ionization is very clear once they re-optimized in their deprotonated species. The significant enzyme inhibition is noted since their energies gain changed in neutral forms from 14.4 and 27.3 Kcal/mol to 39.7 and 29.4 Kcal/mol of the deprotonated species, respectively.
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