Exploring novel and potent molecules for disrupting DEPTOR-mTOR interaction through structure-steered screening, extra-exactitude molecular docking, prime binding free energy estimation and voguish molecular dynamics

References

• Bowers, K. J., Chow, D. E., Xu, H., Dror, R. O., Eastwood, M. P., Gregersen, B. A., Klepeis, J. L., Kolossvary, I., Moraes, M. A., Sacerdoti, F. D., Salmon, J. K., Shan, Y., & Shaw, D. E. (2006). Scalable algorithms for molecular dynamics simulations on commodity clusters. SC '06: Proceedings of the 2006 ACM/IEEE Conference on Supercomputing (pp. 43-43). https://doi.org/10.1109/SC.2006.54.
   Google Scholar
• Caron, A., Briscoe, D. M., Richard, D., & Laplante, M. (2018). DEPTOR at the nexus of cancer, metabolism, and immunity. Physiological Reviews, 98(3), 1765–1803. https://doi.org/10.1152/physrev.00064.2017
   PubMed Web of Science ®Google Scholar
• Catena, V., & Fanciulli, M. (2017). Deptor: Not only a mTOR inhibitor. Journal of Experimental & Clinical Cancer Research, 36(1), 12. https://doi.org/10.1186/s13046-016-0484-y
   Google Scholar
• Chen, J., Zhu, H., Liu, Q., Ning, D., Zhang, Z., Zhang, L., Mo, J., Du, P., Liu, X., Song, S., Fan, Y., Liang, H., Liu, J., Zhang, B., & Chen, X. (2019). DEPTOR induces a partial epithelial-to-mesenchymal transition and metastasis via autocrine TGFβ1 signaling and is associated with poor prognosis in hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research, 38(1), 273. https://doi.org/10.1186/s13046-019-1220-1
   PubMedGoogle Scholar
• Di Micco, S., Musella, S., Scala, M. C., Sala, M., Campiglia, P., Bifulco, G., & Fasano, A. (2021). In silico analysis revealed potential anti-SARS-CoV-2 main protease activity by the zonulin inhibitor larazotide acetate. Frontiers in Chemistry, 8.
   Google Scholar
• Duan, S., Skaar, J. R., Kuchay, S., Toschi, A., Kanarek, N., Ben-Neriah, Y., & Pagano, M. (2011). mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Molecular Cell, 44(2), 317–324. https://doi.org/10.1016/j.molcel.2011.09.005
   PubMed Web of Science ®Google Scholar
• El Khoury, L., Santos-Martins, D., Sasmal, S., Eberhardt, J., Bianco, G., Ambrosio, F. A., Solis-Vasquez, L., Koch, A., Forli, S., & Mobley, D. L. (2019). Comparison of affinity ranking using AutoDock-GPU and MM-GBSA scores for BACE-1 inhibitors in the D3R Grand Challenge 4. Journal of Computer-Aided Molecular Design, 33(12), 1011–1020. https://doi.org/10.1007/s10822-019-00240-w
   PubMed Web of Science ®Google Scholar
• Evans, D. J., & Holian, B. L. (1985). The Nose–Hoover thermostat. The Journal of Chemical Physics, 83(8), 4069–4074. https://doi.org/10.1063/1.449071
   Web of Science ®Google Scholar
• Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry, 49(21), 6177–6196. https://doi.org/10.1021/jm051256o
   PubMed Web of Science ®Google Scholar
• Ganai, S. A. (2021). Characterizing binding intensity and energetic features of histone deacetylase inhibitor pracinostat towards class I HDAC isozymes through futuristic drug designing strategy. In Silico Pharmacol, 9, 18.
   PubMedGoogle Scholar
• Ganai, S. A., Abdullah, E., Rashid, R., & Altaf, M. (2017). Combinatorial in silico strategy towards identifying potential hotspots during inhibition of structurally identical HDAC1 and HDAC2 enzymes for effective chemotherapy against neurological disorders. Frontiers in Molecular Neuroscience, 10(357).
   PubMedGoogle Scholar
• Ganai, S. A., Farooq, Z., Banday, S., & Altaf, M. (2018). In silico approaches for investigating the binding propensity of apigenin and luteolin against class I HDAC isoforms. Future Medicinal Chemistry, 10(16), 1925–1945. https://doi.org/10.4155/fmc-2018-0020
   PubMed Web of Science ®Google Scholar
• Heo, L., Park, H., & Seok, C. (2013). GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Research, 41(3).
   PubMedGoogle Scholar
• Hou, T., Wang, J., Li, Y., & Wang, W. (2011). Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. Journal of Chemical Information and Modeling, 51(1), 69–82. https://doi.org/10.1021/ci100275a
   PubMed Web of Science ®Google Scholar
• Kuriata, A., Gierut, A. M., Oleniecki, T., Ciemny, Maciej, P., Kolinski, A., Kurcinski, M., & Kmiecik, S. (2018). CABS-flex 2.0: A web server for fast simulations of flexibility of protein structures. Nucleic Acids Research, 46(W1), W338–W343. https://doi.org/10.1093/nar/gky356
   PubMed Web of Science ®Google Scholar
• Labbé, C. M., Rey, J., Lagorce, D., Vavruša, M., Becot, J., Sperandio, O., Villoutreix, B. O., Tufféry, P., & Miteva, M. A. (2015). MTiOpenScreen: A web server for structure-based virtual screening. Nucleic Acids Research, 43(W1), W448–W454. https://doi.org/10.1093/nar/gkv306
   PubMed Web of Science ®Google Scholar
• Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26(2), 283–291. https://doi.org/10.1107/S0021889892009944
   Web of Science ®Google Scholar
• Lee, G. R., Heo, L., & Seok, C. (2016). Effective protein model structure refinement by loop modeling and overall relaxation. Proteins, 1, 293–301.
   Google Scholar
• Lee, J., Shi, Y., Vega, M., Yang, Y., Gera, J., Jung, M. E., & Lichtenstein, A. (2017). Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction. Bioorganic & Medicinal Chemistry Letters, 27(20), 4714–4724. https://doi.org/10.1016/j.bmcl.2017.09.002
   PubMed Web of Science ®Google Scholar
• Li, J., Kim, S. G., & Blenis, J. (2014). Rapamycin: One drug, many effects. Cell Metabolism, 19(3), 373–379. https://doi.org/10.1016/j.cmet.2014.01.001
   PubMed Web of Science ®Google Scholar
• Lovell, S. C., Davis, I. W., Arendall, W. B., III, de Bakker, P. I., Word, J. M., Prisant, M. G., Richardson, J. S., & Richardson, D. C. (2003). Structure validation by Calpha geometry: Phi,psi and Cbeta deviation. Proteins: Structure, Function, and Bioinformatics, 50(3), 437–450. https://doi.org/10.1002/prot.10286
   PubMed Web of Science ®Google Scholar
• Martyna, G. J., Tobias, D. J., & Klein, M. L. (1994). Constant pressure molecular dynamics algorithms. The Journal of Chemical Physics, 101(5), 4177–4189. https://doi.org/10.1063/1.467468
   Web of Science ®Google Scholar
• Meng, X.-Y., Zhang, H.-X., Mezei, M., & Cui, M. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer-Aided Drug Design, 7(2), 146–157. https://doi.org/10.2174/157340911795677602
   PubMed Web of Science ®Google Scholar
• Mir, M. A., Ganai, S. A., Mansoor, S., Jan, S., Mani, P., Masoodi, K. Z., Amin, H., Rehman, M. U., & Ahmad, P. (2020). Isolation, purification and characterization of naturally derived Crocetin beta-d-glucosyl ester from Crocus sativus L. against breast cancer and its binding chemistry with ER-alpha/HDAC2. Saudi Journal of Biological Sciences, 27(3), 975–984. https://doi.org/10.1016/j.sjbs.2020.01.018
   PubMed Web of Science ®Google Scholar
• Morales-Martinez, M., Lichtenstein, A., & Vega, M. I. (2021). Function of Deptor and its roles in hematological malignancies. Aging, 13(1), 1528–1564. https://doi.org/10.18632/aging.202462
   PubMedGoogle Scholar
• Morris, A. L., MacArthur, M. W., Hutchinson, E. G., & Thornton, J. M. (1992). Stereochemical quality of protein structure coordinates. Proteins, 12(4), 345–364.
   PubMed Web of Science ®Google Scholar
• Peterson, T. R., Laplante, M., Thoreen, C. C., Sancak, Y., Kang, S. A., Kuehl, W. M., Gray, N. S., & Sabatini, D. M. (2009). DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell, 137(5), 873–886. https://doi.org/10.1016/j.cell.2009.03.046
   PubMed Web of Science ®Google Scholar
• Prajapat, R., Marwal, A., & Gaur, R. K. (2014). Recognition of errors in the refinement and validation of three-dimensional structures of AC1 proteins of begomovirus strains by using ProSA-Web. Journal of Viruses, 2014, 1–6. https://doi.org/10.1155/2014/752656
   Google Scholar
• Ramachandran, G. N., Ramakrishnan, C., & Sasisekharan, V. (1963). Stereochemistry of polypeptide chain configurations. Journal of Molecular Biology, 7, 95–99.
   PubMed Web of Science ®Google Scholar
• Reynès, C., Host, H., Camproux, A.-C., Laconde, G., Leroux, F., Mazars, A., Deprez, B., Fahraeus, R., Villoutreix, B. O., & Sperandio, O. (2010). Designing focused chemical libraries enriched in protein-protein interaction inhibitors using machine-learning methods. PLoS Computational Biology, 6(3), e1000695. https://doi.org/10.1371/journal.pcbi.1000695
   PubMed Web of Science ®Google Scholar
• Sastry, G. M., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3), 221–234. https://doi.org/10.1007/s10822-013-9644-8
   PubMed Web of Science ®Google Scholar
• Saxton, R. A., & Sabatini, D. M. (2017). mTOR signaling in growth, metabolism, and disease. Cell, 168(6), 960–976. https://doi.org/10.1016/j.cell.2017.02.004
   PubMed Web of Science ®Google Scholar
• Shankaran, K. S., Ganai, S. A., Arun, K. P., Brindha, P., & Mahadevan, V. (2017). In silico and In vitro evaluation of the anti-inflammatory potential of Centratherum punctatum Cass-A. Journal of Biomolecular Structure & Dynamics, 35(4), 765–780. https://doi.org/10.1080/07391102.2016.1160840
   PubMed Web of Science ®Google Scholar
• Shelley, J. C., Cholleti, A., Frye, L. L., Greenwood, J. R., Timlin, M. R., & Uchimaya, M. (2007). Epik: A software program for pK( a ) prediction and protonation state generation for drug-like molecules. Journal of Computer-Aided Molecular Design, 21(12), 681–691. https://doi.org/10.1007/s10822-007-9133-z
   PubMed Web of Science ®Google Scholar
• Shi, Y., Daniels-Wells, T. R., Frost, P., Lee, J., Finn, R. S., Bardeleben, C., Penichet, M. L., Jung, M. E., Gera, J. & Lichtenstein, A. (2016). Cytotoxic Properties of a DEP TOR-mTOR Inhibitor in Multiple Myeloma Cells. Cancer Res, 76, 5822–5831.
   Google Scholar
• Sippl, M. J. (1993). Recognition of errors in three-dimensional structures of proteins. Proteins, 17(4), 355–362. https://doi.org/10.1002/prot.340170404
   PubMed Web of Science ®Google Scholar
• Srinivasan, P., Chella Perumal, P., & Sudha, A. (2014). Discovery of novel inhibitors for nek6 protein through homology model assisted structure based virtual screening and molecular docking approaches. The Scientific World Journal, 2014, 1–9. https://doi.org/10.1155/2014/967873
   Google Scholar
• Teh, A. H., Yeap, K. H., & Hisano, T. (2020). Insights into DEPTOR regulation from in silico analysis of DEPTOR complexes. Journal of Structural Biology, 212(2), 107602. https://doi.org/10.1016/j.jsb.2020.107602
   PubMed Web of Science ®Google Scholar
• Tripathi, S. K., Muttineni, R., & Singh, S. K. (2013). Extra precision docking, free energy calculation and molecular dynamics simulation studies of CDK2 inhibitors. Journal of Theoretical Biology, 334, 87–100. https://doi.org/10.1016/j.jtbi.2013.05.014
   PubMed Web of Science ®Google Scholar
• Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
   PubMed Web of Science ®Google Scholar
• Varusai, T. M., & Nguyen, L. K. (2018). Dynamic modelling of the mTOR signalling network reveals complex emergent behaviours conferred by DEPTOR. Scientific Reports, 8(1), 643. https://doi.org/10.1038/s41598-017-18400-z
   PubMedGoogle Scholar
• Vilar, S., Karpiak, J., & Costanzi, S. (2010). Ligand and structure-based models for the prediction of ligand-receptor affinities and virtual screenings: Development and application to the beta(2)-adrenergic receptor. Journal of Computational Chemistry, 31(4), 707–720. https://doi.org/10.1002/jcc.21346
   PubMed Web of Science ®Google Scholar
• Wang, Z., Zhong, J., Inuzuka, H., Gao, D., Shaik, S., Sarkar, F. H., & Wei, W. (2012). An evolving role for DEPTOR in tumor development and progression. Neoplasia, 14(5), 368–375. https://doi.org/10.1593/neo.12542
   PubMed Web of Science ®Google Scholar
• Wiederstein, M., & Sippl, M. J. (2007). ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 35, W407–W410. https://doi.org/10.1093/nar/gkm290
   PubMed Web of Science ®Google Scholar
• Wu, S., & Zhang, Y. (2007). LOMETS: A local meta-threading-server for protein structure prediction. Nucleic Acids Research, 35(10), 3375–3382. https://doi.org/10.1093/nar/gkm251
   PubMed Web of Science ®Google Scholar
• Zhang, Y. (2008). I-TASSER server for protein 3D structure prediction. BMC Bioinformatics, 9(1), 1471–2105. https://doi.org/10.1186/1471-2105-9-40
   Google Scholar
• Zhang, Y., & Skolnick, J. (2004). SPICKER: A clustering approach to identify near-native protein folds. Journal of Computational Chemistry, 25(6), 865–871. https://doi.org/10.1002/jcc.20011
   PubMed Web of Science ®Google Scholar
• Zhao, Y., Xiong, X., & Sun, Y. (2011). DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular Cell, 44(2), 304–316. https://doi.org/10.1016/j.molcel.2011.08.029
   PubMed Web of Science ®Google Scholar