Computational Design of some Piperine Derivatives as Novel Survivin Inhibitors

In the first part of this study, two of the most potent docking programs, AutoDock and AutoDock Vina,have been selected for virtual screening of a library of 2497 commercially available drug like derivativesof Piperine. Since AutoDock Vina is faster than AutoDock, first of all, the selected compounds weredocked into the binding site of Survivin by using AutoDock Vina program. Based on the predictedbinding energies, the compounds were ranked and the top 100 compounds were selected for morescreening using AutoDock program. Considering the obtained binding energies, the top two highestranked compounds, as well as Piperine, were selected and subjected to a 10 ns molecular dynamicssimulation for further validate the proposed binding modes and interactions. In the last part of this study,the binding free energies were calculated using the MMPBSA and MMGBSA methods. Moreovernormal-mode analyses were carried out using the nabnmode module of AMBER in order to estimate theconformational entropy (TΔS) to binding free energies. In addition to MMBP-GBSA methods, by usingalanine scanning, ten residues in the active site of Survivin were systematically substituted with alanineand subsequently assayed to evaluate the contribution of each residue to the total binding free energy inorder to determine the critical and noncritical residues in the active site.

کلیدواژه ها:

Survivin ، Piperine ، Anticancer Drug ، Molecular Docking ، Virtual Screening ، Molecular DynamicsSimulation