MOLECULAR MODELLING AND DOCKING STUDIES OF HUMAN ACROSIN BINDING PROTEIN (ACRBP/OY-TES-1)
Objective: We have made an attempt to identify inhibitors that are bound with Acrosin binding protein (ACRBP/OY-TES-1) through In silico molecular docking studies.
Methods: Modeling of ACRBP/OY-TES-1 was performed using Iterative Threading Assembly Refinement (I-TASSER) software. Docking calculations were carried out using Glide. Glide Score (GS core) was used to rank the ligands on the basis of their relative binding affinities.
Results: Food and Drug Administration (FDA)-approved drugs were docked with ACRBP/OY-TES-1 to identify potent inhibitors. Leuprolide a decapeptide interacts with the protein at residues Tyr116, Gly421, Leu433, Asp480 and Gln483 with Glide score-14.188. Other compounds that showed high affinity to the protein are triptorelin, nafatarelin, goserelin and sincalide.
Conclusion: The investigation concluded that these drugs could be used as potential inhibitors against ACRBP/OY-TES-1 in cancer treatment.
2. Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007;26:3291-310.
3. Hanzlik RP, Fang J, Koen YM. Filling and mining the reactive metabolite target protein database. Chem Biol Interact 2009;179:38-44.
4. Chan SY, Loscalzo J. The emerging paradigm of network medicine in the study of human disease. Circ Res 2012;111:359-74.
5. YÄ±ldÄ±rÄ±m MA, Goh KI, Cusick ME, BarabÃ¡si AL, Vidal M. Drug-target network. Nat Biotechnol 2007;25:1119-26.
6. Hoelder S, Clarke PA, Workman P. Discovery of small molecule cancer drugs: Successes, challenges and opportunities. Mol Oncol 2012;6:155-76.
7. Makley LN, Gestwicki JE. Expanding the number of Druggableâ€ Targets: non-enzymes and protein-protein interactions. Chem Biol Drug Des 2013;81:22-32.
8. Tejasvi K, Mayuresh A, Gauri T, Venkatesan GK, Krishnan K. In silico molecular docking of marine drugs against cancer proteins. Adv Chem Sci 2013;2:24-8.
9. Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, et al. Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci 2001;98:3282-7.
10. Tammela J, Uenaka A, Ono T, Noguchi Y, Jungbluth AA, Mhawech-Fauceglia P, et al. OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer. Int J Oncol 2006;29:903-10.
11. Luo B, Yun X, Fan R, Lin YD, He SJ, Zhang QM, et al. Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters. Int J Clin Exp Pathol 2013;6:2835-45.
12. Whitehurst AW, Xie Y, Purinton SC, Cappell KM, Swanik JT, Larson B, et al. Tumor antigen acrosin binding protein normalizes mitotic spindle function to promote cancer cell proliferation. Cancer Res 2010;70:7652-61.
13. BrÃ¼ning-Richardson A, Bond J, Alsiary R, Richardson J, Cairns DA, McCormac L et al. NuMA overexpression in epithelial ovarian cancer. PLoS One 2012;7:e38945. doi: 10.1371/journal.pone.0038945. [Article in Press]
14. Abagyan R, Totrov M. High-throughput docking for lead generation. Curr Opin Chem Biol 2001;5:375-82.
15. Wu ST, Zhang Y. LOMETS: A local meta-threading-server for protein structure prediction. Nucleic Acids Res 2007;35:3375-82.
16. Zhang Y, Skolnick J. Automated structure prediction of weakly homologous proteins on a genomic scale. Proc Natl Acad Sci 2004;101:7594-9.
17. Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER Suite: protein structure and function prediction. Nat Methods 2015;12:7-8.
18. Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 2010;5:725-38.
19. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 2008;9:40. doi: 10.1186/1471-2105-9-40. [Article in Press]
20. Halgren T. New method for fast and accurate binding-site identification and analysis. Chem Biol Drug Des 2007;69:146-8.
21. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, et al. Glide: a new approach for rapid, Accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 2004;47:1750-9.
22. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy. J Med Chem 2004;47:1739-49.
23. Vilella AJ, Severin J, Ureta-Vidal A, Heng L, Durbin R, Birney E. Ensembl Compara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates. Genome Res 2009;9:327-35.
24. Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A. ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 2003;31:3784-8.
25. Chou PY, Fasman GD. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol 1978;47:45-148.
26. Schultz J, Copley RR, Doerks T, Ponting CP, Bork P. SMART: a web-based tool for the study of genetically mobile domains. Nucleic Acids Res 2000;28:231-4.
27. Cen YH, Guo WW, Luo B, Lin YD, Zhang QM, Zhou SF, et al. Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow-derived mesenchymal stem cells. Cell Biol Int 2012;36:917-22.
28. Schuler G, Steinman RM. Dendritic cells as adjuvants for immune-mediated resistance to tumors. J Exp Med 1997;186:1183-7.
29. Qiu J, Lil GW, Sui YF, Sun YJ, Huang YY, Si SY. Truncated TERT mRNA transfected dendritic cells evoke TERT specific anti tumor response in vivo. Hepatogastroenterology 2007;54:681-7.
30. Fishman MN, Thompson JA, Pennock GK, Gonzalez R, Diez LM, Daud AI, et al. Phase I trial of ALT-801,an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264â€“272)/HLA-A* 0201 complex, in patients with advanced malignancies. Clin Cancer Res 2011;17:7765-75.