Exploring the composition of protein-ligand binding sites for cancerous inhibitor of PP2A (CIP2A) by inhibitor guided binding analysis: paving a new way for the Discovery of drug candidates against triple negative breast cancer (TNBC)

References

• Ren J, Li W, Yan L, et al. Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients’ survival. Br J Cancer. 2011;105(12):1905–1911. doi: 10.1038/bjc.2011.492.
   PubMed Web of Science ®Google Scholar
• Xue Y, Wu G, Wang X, et al. CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma. Med Oncol. 2013;30(1):406. doi: 10.1007/s12032-012-0406-6.
   PubMed Web of Science ®Google Scholar
• Xiao X, He Z, Cao W, et al. Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/akt signaling pathways. Int J Oncol. 2016;48(6):2608–2618. doi: 10.3892/ijo.2016.3488.
   PubMed Web of Science ®Google Scholar
• Junttila MR, Puustinen P, Niemelä M, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130(1):51–62. doi: 10.1016/j.cell.2007.04.044.
   PubMed Web of Science ®Google Scholar
• Li W, Ge Z, Liu C, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14(12):3722–3728. doi: 10.1158/1078-0432.CCR-07-4137.
   PubMed Web of Science ®Google Scholar
• Khanna A, Böckelman C, Hemmes A, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101(11):793–805. doi: 10.1093/jnci/djp103.
   PubMedGoogle Scholar
• Côme C, Laine A, Chanrion M, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15(16):5092–5100. doi: 10.1158/1078-0432.CCR-08-3283.
   PubMed Web of Science ®Google Scholar
• Ma L, Wen ZS, Liu Z, et al. Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer. PLoS One. 2011;6(5):e20159. doi: 10.1371/journal.pone.0020159.
   PubMed Web of Science ®Google Scholar
• Xu D, Wang Q, Gruber A, et al. Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells. Oncogene. 2000;19(45):5123–5133. doi: 10.1038/sj.onc.1203890.
   PubMed Web of Science ®Google Scholar
• Wang J, Okkeri J, Pavic K, et al. Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56. EMBO Rep. 2017;18(3):437–450. doi: 10.15252/embr.201642788.
   PubMed Web of Science ®Google Scholar
• Laine A, Sihto H, Come C, et al. Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1. Cancer Discov. 2013;3(2):182–197. doi: 10.1158/2159-8290.CD-12-0292.
   PubMed Web of Science ®Google Scholar
• Choi YA, Park JS, Park MY, et al. Increase in CIP2A expression is associated with doxorubicin resistance. FEBS Lett. 2011;585(5):755–760. doi: 10.1016/j.febslet.2011.01.018.
   PubMed Web of Science ®Google Scholar
• Walsh EM, Keane MM, Wink DA, et al. Review of triple negative breast cancer and the impact of inducible nitric oxide synthase on tumor biology and patient outcomes. Crit Rev Oncog. 2016;21(5-6):333–351. doi: 10.1615/CritRevOncog.2017021307.
   PubMed Web of Science ®Google Scholar
• Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938–1948. doi: 10.1056/NEJMra1001389.
   PubMed Web of Science ®Google Scholar
• Vagia E, Mahalingam D, Cristofanilli M. The landscape of targeted therapies in TNBC. Cancers (Basel). 2020;12(4):916. doi: 10.3390/cancers12040916.
   PubMed Web of Science ®Google Scholar
• De P, Carlson J, Leyland-Jones B, et al. Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): an oncoprotein with many hands. Oncotarget. 2014;5(13):4581–4602. doi: 10.18632/oncotarget.2127.
   PubMedGoogle Scholar
• Tseng LM, Liu CY, Chang KC, et al. CIP2A is a target of bortezomib in human triple negative breast cancer cells. Breast Cancer Res. 2012;14(2):R68. doi: 10.1186/bcr3175.
   PubMed Web of Science ®Google Scholar
• Liu CY, Hung MH, Wang DS, et al. Tamoxifen induces apoptosis through cancerous inhibitor of protein phosphatase 2A-dependent phospho-Akt inactivation in estrogen receptor-negative human breast cancer cells. Breast Cancer Res. 2014;16(5):431. doi: 10.1186/s13058-014-0431-9.
   PubMed Web of Science ®Google Scholar
• Khanna A, Pimanda JE. Clinical significance of cancerous inhibitor of protein phosphatase 2A in human cancers. Int J Cancer. 2016;138(3):525–532. doi: 10.1002/ijc.29431.
   PubMed Web of Science ®Google Scholar
• Khanna A, Pimanda JE, Westermarck J. Cancerous inhibitor of protein phosphatase 2A, an emerging human oncoprotein and a potential cancer therapy target. Cancer Res. 2013;73(22):6548–6553. doi: 10.1158/0008-5472.CAN-13-1994.
   PubMed Web of Science ®Google Scholar
• Rincón R, Cristóbal I, Zazo S, et al. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects. Oncotarget. 2015;6(6):4299–4314. doi: 10.18632/oncotarget.3012.
   PubMedGoogle Scholar
• Tsukamoto S, Huang Y, Umeda D, et al. 67-kDa laminin receptor-dependent protein phosphatase 2A (PP2A) activation elicits melanoma-specific antitumor activity overcoming drug resistance. J Biol Chem. 2014;289(47):32671–32681. doi: 10.1074/jbc.M114.604983.
   PubMed Web of Science ®Google Scholar
• Holm L, Sander C. Dali/FSSP classification of three-dimensional protein folds. Nucleic Acids Res. 1997;25(1):231–234. doi: 10.1093/nar/25.1.231.
   PubMed Web of Science ®Google Scholar
• Dahlström KM, Salminen TA. 3D model for cancerous inhibitor of protein phosphatase 2A armadillo domain unveils highly conserved protein-protein interaction characteristics. J Theor Biol. 2015;386:78–88. doi: 10.1016/j.jtbi.2015.09.010.
   PubMed Web of Science ®Google Scholar
• Liu CY, Hu MH, Hsu CJ, et al. Lapatinib inhibits CIP2A/PP2A/p-akt signaling and induces apoptosis in triple negative breast cancer cells. Oncotarget. 2016;7(8):9135–9149. doi: 10.18632/oncotarget.7035.
   PubMedGoogle Scholar
• Huang Q, Qin S, Yuan X, et al. Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A. Oncol Rep. 2017;38(1):598–606. doi: 10.3892/or.2017.5667.
   PubMed Web of Science ®Google Scholar
• Liu Z, Ma L, Wen ZS, et al. Cancerous inhibitor of PP2A is targeted by natural compound celastrol for degradation in non-small-cell lung cancer. Carcinogenesis. 2014;35(4):905–914. doi: 10.1093/carcin/bgt395.
   PubMed Web of Science ®Google Scholar
• Lybrand TP. Ligand-protein docking and rational drug design. Curr Opin Struct Biol. 1995;5(2):224–228. doi: 10.1016/0959-440x(95)80080-8.
   PubMed Web of Science ®Google Scholar
• Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci. 2019;20(18):4331. doi: 10.3390/ijms20184331.
   PubMed Web of Science ®Google Scholar
• Wang R, Lu Y, Wang S. Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem. 2003;46(12):2287–2303. doi: 10.1021/jm0203783.
   PubMed Web of Science ®Google Scholar
• Ferrara P, Gohlke H, Price DJ, et al. Assessing scoring functions for protein-ligand interactions. J Med Chem. 2004;47(12):3032–3047. doi: 10.1021/jm030489h.
   PubMed Web of Science ®Google Scholar
• Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res. 2000;28(1):235–242. doi: 10.1093/nar/28.1.235.
   PubMed Web of Science ®Google Scholar
• Maestro S. LLC, New York, NY, 2023.
   Google Scholar
• Shelley JC, Cholleti A, Frye LL, et al. Epik: a software program for pK (a) prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des. 2007;21(12):681–691. doi: 10.1007/s10822-007-9133-z.
   PubMed Web of Science ®Google Scholar
• Olsson MHM, Søndergaard CR, Rostkowski M, et al. PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J Chem Theory Comput. 2011;7(2):525–537. doi: 10.1021/ct100578z.
   PubMed Web of Science ®Google Scholar
• Lu C, Wu C, Ghoreishi D, et al. OPLS4: improving force field accuracy on challenging regimes of chemical space. J Chem Theory Comput. 2021;17(7):4291–4300. doi: 10.1021/acs.jctc.1c00302.
   PubMed Web of Science ®Google Scholar
• Kloostra S. Sitemap. 2015; p. 83–85.
   Google Scholar
• Liu Y, Yang X, Gan J, et al. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022;50(W1):W159–W164. doi: 10.1093/nar/gkac394.
   PubMed Web of Science ®Google Scholar
• Durairaj DR, Shanmughavel P. In silico drug design of thiolactomycin derivatives against Mtb-KasA enzyme to inhibit multidrug resistance of Mycobacterium tuberculosis. Interdiscip Sci. 2019;11(2):215–225. doi: 10.1007/s12539-017-0257-0.
   PubMed Web of Science ®Google Scholar
• Cao Y, Li L. Improved protein-ligand binding affinity prediction by using a curvature-dependent surface-area model. Bioinformatics. 2014;30(12):1674–1680. doi: 10.1093/bioinformatics/btu104.
   PubMed Web of Science ®Google Scholar
• Yang X, Liu Y, Gan J, et al. FitDock: protein-ligand docking by template fitting. Brief Bioinform. 2022;23(3):bbac087. doi: 10.1093/bib/bbac087.
   PubMed Web of Science ®Google Scholar
• Singh M, Rupesh N, Pandit SB, et al. Curcumin inhibits membrane-damaging pore-forming function of the beta-barrel pore-forming toxin vibrio cholerae cytolysin. Front Microbiol. 2021;12:809782. doi: 10.3389/fmicb.2021.809782.
   PubMed Web of Science ®Google Scholar
• Mishra PM, Nandi CK. Structural decoding of a small molecular inhibitor on the binding of SARS-CoV-2 to the ACE 2 receptor. J Phys Chem B. 2021;125(30):8395–8405. doi: 10.1021/acs.jpcb.1c03294.
   PubMed Web of Science ®Google Scholar
• Zhang P, Zhu L, Cai J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020;126(12):1671–1681. doi: 10.1161/CIRCRESAHA.120.317134.
   PubMed Web of Science ®Google Scholar
• Liu Y, Grimm M, Dai WT, et al. CB-Dock: a web server for cavity detection-guided protein-ligand blind docking. Acta Pharmacol Sin. 2020;41(1):138–144. doi: 10.1038/s41401-019-0228-6.
   PubMed Web of Science ®Google Scholar
• Vijayakumar S, Manogar P, Prabhu S, et al. Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for alzheimer’s disease. J Pharm Anal. 2018;8(6):413–420. doi: 10.1016/j.jpha.2017.07.006.
   PubMed Web of Science ®Google Scholar
• Glide S. LLC, New York, NY, 2017.
   Google Scholar
• Koes DR, Baumgartner MP, Camacho CJ. Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise. J Chem Inf Model. 2013;53(8):1893–1904. doi: 10.1021/ci300604z.
   PubMed Web of Science ®Google Scholar
• Hassan NM, Alhossary AA, Mu Y, et al. Protein-ligand blind docking using QuickVina-W with inter-process spatio-temporal integration. Sci Rep. 2017;7(1):15451. doi: 10.1038/s41598-017-15571-7.
   PubMedGoogle Scholar
• Hetényi C, van der Spoel D. Efficient docking of peptides to proteins without prior knowledge of the binding site. Protein Sci. 2002;11(7):1729–1737. doi: 10.1110/ps.0202302.
   PubMed Web of Science ®Google Scholar
• Ghersi D, Sanchez R. Improving accuracy and efficiency of blind protein-ligand docking by focusing on predicted binding sites. Proteins. 2009;74(2):417–424. doi: 10.1002/prot.22154.
   PubMed Web of Science ®Google Scholar
• Case DA, Ben-Shalom IY, Brozell SR, et al. AMBER 2018. San Francisco (CA): University of California; 2018.
   Google Scholar
• Maier JA, Martinez C, Kasavajhala K, et al. ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput. 2015;11(8):3696–3713. doi: 10.1021/acs.jctc.5b00255.
   PubMed Web of Science ®Google Scholar
• Wang J, Wolf RM, Caldwell JW, et al. Development and testing of a general amber force field. J Comput Chem. 2004;25(9):1157–1174. doi: 10.1002/jcc.20035.
   PubMed Web of Science ®Google Scholar
• Salomon-Ferrer R, Case DA, Walker RC. An overview of the amber biomolecular simulation package. WIREs Comput Mol Sci. 2013;3(2):198–210. doi: 10.1002/wcms.1121.
   Web of Science ®Google Scholar
• Akinsiku OE, Soremekun OS, Olotu FA, et al. Exploring the role of Asp1116 in selective drug targeting of CREBcAMP- Responsive element-binding protein implicated in prostate cancer. Comb Chem High Throughput Screen. 2020;23(3):178–184. doi: 10.2174/1386207323666200219122057.
   PubMed Web of Science ®Google Scholar
• Jorgensen WL, Chandrasekhar J, Madura JD, et al. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79(2):926–935. doi: 10.1063/1.445869.
   Web of Science ®Google Scholar
• Roe DR, Cheatham TE. 3rd, PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–3095. doi: 10.1021/ct400341p.
   PubMed Web of Science ®Google Scholar
• Dassault Systèmes BIOVIA. Discovery studio visualize, version 2019; San Diego (CA): Dassault Systèmes; 2019.
   Google Scholar
• Kollman PA, Massova I, Reyes C, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res. 2000;33(12):889–897. doi: 10.1021/ar000033j.
   PubMed Web of Science ®Google Scholar
• Broomhead NK, Soliman ME. Can We rely on computational predictions to correctly identify ligand binding sites on novel protein drug targets? Assessment of binding site prediction methods and a protocol for validation of predicted binding sites. Cell Biochem Biophys. 2017;75(1):15–23. doi: 10.1007/s12013-016-0769-y.
   PubMed Web of Science ®Google Scholar
• Olanlokun JO, Olotu FA, Idowu OT, et al. In vitro, in silico studies of newly isolated tetrahydro-4-(7-hydroxy-10-methoxy-6, 14-dimethyl-15-m-tolylpentadec-13-enyl) pyran-2-one and isobutyryl acetate compounds from alstonia boonei stem bark. J Mol Struct. 2020;1216:128225. doi: 10.1016/j.molstruc.2020.128225.
   Web of Science ®Google Scholar
• Bahadur RP, Zacharias M. The interface of protein-protein complexes: analysis of contacts and prediction of interactions. Cell Mol Life Sci. 2008;65(7–8):1059–1072. doi: 10.1007/s00018-007-7451-x.
   PubMed Web of Science ®Google Scholar
• Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron. 2018;99(6):1129–1143. doi: 10.1016/j.neuron.2018.08.011.
   PubMed Web of Science ®Google Scholar
• Chen J, Zeng Q, Wang W, et al. Decoding the identification mechanism of an SAM-III riboswitch on ligands through multiple independent Gaussian-Accelerated molecular dynamics simulations. J Chem Inf Model. 2022;62(23):6118–6132. doi: 10.1021/acs.jcim.2c00961.
   PubMedGoogle Scholar
• Chen J, Wang X, Pang L, et al. Effect of mutations on binding of ligands to guanine riboswitch probed by free energy perturbation and molecular dynamics simulations. Nucleic Acids Res. 2019;47(13):6618–6631. doi: 10.1093/nar/gkz499.
   PubMed Web of Science ®Google Scholar
• Martínez L. Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS ONE. 2015;10(3):e0119264. doi: 10.1371/journal.pone.0119264.
   PubMed Web of Science ®Google Scholar