Molecular docking analysis of aplysin analogs targeting survivin protein.

Abstract

Survivin (IAP proteins) remains an important target for anticancer drug development as it is reported to be over-expressed in tumor cells to enhance resistance to apoptotic stimuli. The study focuses on virtual screening of marine compounds inhibiting survivin, a multifunctional protein, using a computational approach. Structures of compounds were prepared using ChemDraw Ultra 10. Software and converted into its 3D PDB structure and its energy was minimized using Discovery Studio client 2.5. The target protein, survivin was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling was carried out on marine compounds and the filtered compounds were further promoted for molecular docking analysis and interaction studies using AutoDock Tools 4.0. Molecular docking results revealed that analog (AP 4) of Aplysin, showed very promising inhibitory potential against survivin with a binding energy of -8.75 kcal/mol and Ki 388.28 nM as compared to its known inhibitor, Celecoxib having binding energy of -6.65 kcal/mol and Ki 13.43 μM. AP 4. The analog depicted similarity in pattern when compared to standard. The result proposes AP 4, is an effective molecule exhibiting prominent potential to inhibit survivin and thus promoting apoptosis in tumor cells.

• Authors: Eram Shakeel, Salman Akhtar, Mohd Kalim Ahmad Khan, Mohtashim Lohani, Jamal M Arif, Mohd Haris Siddiqui
• Journal: Bioinformation (Bioinformation) Vol. 13 Issue 9 Pg. 293-300 ( 2017) ISSN: 0973-2063 [Print] Singapore
• PMID: 29081608 (Publication Type: Journal Article)