273
Views
1
CrossRef citations to date
0
Altmetric
Research Articles

Structure-based design of small molecule and peptide inhibitors for selective targeting of ROCK1: an integrative computational approach

&
Pages 7450-7468 | Received 09 Oct 2020, Accepted 26 Feb 2021, Published online: 10 Mar 2021

References

  • Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindah, E. (2015). Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1-2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
  • Amadei, A., Ceruso, M. A., & Nola, A. D. (1999). On the convergence of the conformational coordinates basis set obtained by the essential dynamics analysis of proteins’ molecular dynamics simulations. Proteins: Structure, Function, and Genetics, 36(4), 419–424. https://doi.org/10.1002/(SICI)1097-0134(19990901)36:4<419::AID-PROT5>3.0.CO;2-U
  • Ansar, S., & Vetrivel, U. (2019). PepVis: An integrated peptide virtual screening pipeline for ensemble and flexible docking protocols. Chemical Biology & Drug Design, 94(6), 2041–2050. https://doi.org/10.1111/cbdd.13607
  • Ansar, S., & Vetrivel, U. (2020). KinomeRun: An interactive utility for kinome target screening and interaction fingerprint analysis towards holistic visualization on kinome tree. Chemical Biology & Drug Design, 96(4), 1162–1175. https://doi.org/10.1111/cbdd.13705
  • Berrino, E., & Supuran, C. T. (2019). Rho-kinase inhibitors in the management of glaucoma. Expert Opinion on Therapeutic Patents, 29(10), 817–827. https://doi.org/10.1080/13543776.2019.1670812
  • Bhojwani, H. R., & Joshi, U. J. (2019). Selecting protein structure/s for docking-based virtual screening: A case study on type II inhibitors of VEGFR-2 kinase. International Journal of Pharmaceutical Sciences and Research, 10(6), 2998–3011. https://doi.org/10.13040/IJPSR.0975-8232.10(6).2998-11
  • Chartier, M., Chénard, T., Barker, J., & Najmanovich, R. (2013). Kinome render: A stand-alone and web-accessible tool to annotate the human protein kinome tree. PeerJ, 1(1), e126. https://doi.org/10.7717/peerj.126
  • Chen, H., Li, S., Hu, Y., Chen, G., Jiang, Q., Tong, R., Zang, Z., & Cai, L. (2016). An integrated in silico method to discover novel Rock1 inhibitors: Multi-complex-based pharmacophore, molecular dynamics simulation and hybrid protocol virtual screening. Combinatorial Chemistry & High Throughput Screening, 19(1), 36–50. https://doi.org/10.2174/1386207319666151203001946
  • Chohan, T. A., Qian, H., Pan, Y., & Chen, J.-Z. (2015). Cyclin-dependent kinase-2 as a target for cancer therapy: Progress in the development of CDK2 inhibitors as anti-cancer agents. Current Medicinal Chemistry, 22(2), 237–263. https://doi.org/10.2174/0929867321666141106113633
  • Elhady, A. K., Abdel-Halim, M., Abadi, A. H., & Engel, M. (2017). Development of selective Clk1 and -4 inhibitors for cellular depletion of cancer-relevant proteins. Journal of Medicinal Chemistry, 60(13), 5377–5391. https://doi.org/10.1021/acs.jmedchem.6b01915
  • Emmanouilidi, A., & Falasca, M. (2017). Targeting PDK1 for chemosensitization of cancer cells. Cancers, 9(12), 140. https://doi.org/10.3390/cancers9100140
  • Eswar, N., Webb, B., Marti‐Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M‐y., Pieper, U., & Sali, A. (2006). Comparative protein structure modeling using modeller. Current Protocols in Bioinformatics, 15(1), 5.6.1–5.6.30. https://doi.org/10.1002/0471250953.bi0506s15
  • Fiore, M., Forli, S., & Manetti, F. (2016). Targeting mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2, MK2): Medicinal chemistry efforts to lead small molecule inhibitors to clinical trials. Journal of Medicinal Chemistry, 59(8), 3609–3634. https://doi.org/10.1021/acs.jmedchem.5b01457
  • Gill, K., Nigam, L., Singh, R., Kumar, S., Subbarao, N., Chauhan, S. S., & Dey, S. (2014). The rational design of specific peptide inhibitor against p38α MAPK at allosteric-site: A therapeutic modality for HNSCC. PLoS One, 9(7), e101525. https://doi.org/10.1371/journal.pone.0101525
  • Gill, K., Singh, A. K., Kapoor, V., Nigam, L., Kumar, R., Holla, P., Das, S. N., Yadav, S., Subbarao, N., Mohanti, B. K., & Dey, S. (2013). Development of peptide inhibitor as a therapeutic agent against head and neck squamous cell carcinoma (HNSCC) targeting p38α MAP kinase. Biochimica et Biophysica Acta, 1830(3), 2763–2769. https://doi.org/10.1016/j.bbagen.2012.12.001
  • Haque, S., & Morris, J. C. (2017). Transforming growth factor-β: A therapeutic target for cancer. Human Vaccines & Immunotherapeutics, 13(8), 1741–1750. https://doi.org/10.1080/21645515.2017.1327107
  • Hess, B., Bekker, H., Berendsen, H. J. C., & Fraaije, J. G. E. M. (1997). LINCS: A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18(12), 1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5
  • Ionescu, A., Dufrasne, F., Gelbcke, M., Jabin, I., Kiss, R., & Lamoral-Theys, D. (2012). DYRK1A kinase inhibitors with emphasis on cancer. Mini Reviews in Medicinal Chemistry, 12(13), 1315–1329. https://doi.org/10.2174/13895575112091315
  • Jacobs, M., Hayakawa, K., Swenson, L., Bellon, S., Fleming, M., Taslimi, P., & Doran, J. (2006). The structure of dimeric ROCK I reveals the mechanism for ligand selectivity. The Journal of Biological Chemistry, 281(1), 260–268. https://doi.org/10.1074/jbc.M508847200
  • Keretsu, S., Bhujbal, S. P., & Joo Cho, S. (2019). Computational study of paroxetine-like inhibitors reveals new molecular insight to inhibit GRK2 with selectivity over ROCK1. Scientific Reports, 9(1), 1–14. https://doi.org/10.1038/s41598-019-48949-w
  • Kooistra, A. J., Kanev, G. K., van Linden, O. P. J., Leurs, R., de Esch, I. J. P., & Graaf, C. (2016). KLIFS: A structural kinase-ligand interaction database. Nucleic Acids Research, 44(D1), D365–D371. https://doi.org/10.1093/nar/gkv1082
  • Lätti, S., Niinivehmas, S., & Pentikäinen, O. T. (2016). Rocker: Open source, easy-to-use tool for AUC and enrichment calculations and ROC visualization. Journal of Cheminformatics, 8(1), 45. https://doi.org/10.1186/s13321-016-0158-y
  • Liu, J., Lu, Y., Li, G., Xiao, M., Yang, G., & Pan, Y. (2021). Elucidation the binding mechanism of Nelumbo nucifera-derived isoquinoline alkaloids as Rho-kinase 1 inhibitors by molecular docking and dynamic simulation. Journal of Biomolecular Structure & Dynamics, 39(2), 379–394. https://doi.org/10.1080/07391102.2020.1714484
  • Lountos, G. T., Jobson, A. G., Tropea, J. E., Self, C. R., Zhang, G., Pommier, Y., Shoemaker, R. H., & Waugh, D. S. (2011). Structural characterization of inhibitor complexes with checkpoint kinase 2 (Chk2), a drug target for cancer therapy. Journal of Structural Biology, 176(3), 292–301. https://doi.org/10.1016/j.jsb.2011.09.008
  • Macarulla, T., Ramos, F., & Tabernero, J. (2008). Aurora kinase family: A new target for anticancer drug. Recent Patents on anti-Cancer Drug Discovery, 3(2), 114–122. https://doi.org/10.2174/157489208784638785
  • Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002). The protein kinase complement of the human genome. Science, 298(5600), 1912–1934. https://doi.org/10.1126/science.1075762
  • Merkel, A. L., Meggers, E., & Ocker, M. (2012). PIM1 kinase as a target for cancer therapy. Expert Opinion on Investigational Drugs, 21(4), 425–436. https://doi.org/10.1517/13543784.2012.668527
  • Mysinger, M. M., Carchia, M., Irwin, J. J., & Shoichet, B. K. (2012). Directory of useful decoys, enhanced (DUD-E): Better ligands and decoys for better benchmarking. Journal of Medicinal Chemistry, 55(14), 6582–6594. https://doi.org/10.1021/jm300687e
  • Nakagawa, O., Fujisawa, K., Ishizaki, T., Saito, Y., Nakao, K., & Narumiya, S. (1996). ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Letters, 392(2), 189–193. https://doi.org/10.1016/0014-5793(96)00811-3
  • Nitulescu, G. M., Van De Venter, M., Nitulescu, G., Ungurianu, A., Juzenas, P., Peng, Q., Olaru, O. T., Grădinaru, D., Tsatsakis, A., Tsoukalas, D., Spandidos, D. A., & Margina, D. (2018). The Akt pathway in oncology therapy and beyond (Review). International Journal of Oncology, 53(6), 2319–2331. https://doi.org/10.3892/ijo.2018.4597
  • Nogués, L., Reglero, C., Rivas, V., Neves, M., Penela, P., & Mayor, F. (2017). G-protein-coupled receptor kinase 2 as a potential modulator of the hallmarks of cancer. Molecular Pharmacology, 91(3), 220–228. https://doi.org/10.1124/mol.116.107185
  • O’Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of Cheminformatics, 3(1), 33. https://doi.org/10.1186/1758-2946-3-33
  • Palorini, R., Votta, G., Pirola, Y., De Vitto, H., De Palma, S., Airoldi, C., Vasso, M., Ricciardiello, F., Lombardi, P. P., Cirulli, C., Rizzi, R., Nicotra, F., Hiller, K., Gelfi, C., Alberghina, L., & Chiaradonna, F. (2016). Protein kinase A activation promotes cancer cell resistance to glucose starvation and anoikis. PLoS Genetics, 12(3), e1005931. https://doi.org/10.1371/journal.pgen.1005931
  • Porębska, N., Latko, M., Kucińska, M., Zakrzewska, M., Otlewski, J., & Opaliński, Ł. (2018). Targeting cellular trafficking of fibroblast growth factor receptors as a strategy for selective cancer treatment. Journal of Clinical Medicine, 8(1), 7. https://doi.org/10.3390/jcm8010007
  • Porta, R., Borea, R., Coelho, A., Khan, S., Araújo, A., Reclusa, P., Franchina, T., Van Der Steen, N., Van Dam, P., Ferri, J., Sirera, R., Naing, A., Hong, D., & Rolfo, C. (2017). FGFR a promising druggable target in cancer: Molecular biology and new drugs. Critical Reviews in Oncology/Hematology, 113, 256–267. https://doi.org/10.1016/j.critrevonc.2017.02.018
  • Raveh, B., London, N., & Schueler-Furman, O. (2010). Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins, 78(9), 2029–2040. https://doi.org/10.1002/prot.22716
  • RDKit. (2019). Retrieved March 3, 2020, from http://www.rdkit.org/
  • Riento, K., & Ridley, A. J. (2003). Rocks: Multifunctional kinases in cell behaviour. Nature Reviews. Molecular Cell Biology, 4(6), 446–456. https://doi.org/10.1038/nrm1128
  • Roskoski, R. (2019). Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacological Research, 144, 19–50. https://doi.org/10.1016/j.phrs.2019.03.006
  • Salentin, S., Schreiber, S., Haupt, V. J., Adasme, M. F., & Schroeder, M. (2015). PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Research, 43(W1), W443–W447. https://doi.org/10.1093/nar/gkv315
  • Samdani, A., & Vetrivel, U. (2018). POAP: A GNU parallel based multithreaded pipeline of open babel and AutoDock suite for boosted high throughput virtual screening. Computational Biology and Chemistry, 74, 39–48. https://doi.org/10.1016/j.compbiolchem.2018.02.012
  • Schüttelkopf, A. W., & Van Aalten, D. M. F. (2004). PRODRG: A tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallographica. Section D, Biological Crystallography, 60(Pt 8), 1355–1363. https://doi.org/10.1107/S0907444904011679
  • Shen, M., Tian, S., Pan, P., Sun, H., Li, D., Li, Y., Zhou, H., Li, C., Lee, S. M.-Y., & Hou, T. (2015). Discovery of novel ROCK1 inhibitors via integrated virtual screening strategy and bioassays. Scientific Reports, 5(1), 16749. https://doi.org/10.1038/srep16749
  • Shen, M., Zhou, S., Li, Y., Pan, P., Zhang, L., & Hou, T. (2013). Discovery and optimization of triazine derivatives as ROCK1 inhibitors: Molecular docking, molecular dynamics simulations and free energy calculations. Molecular BioSystems, 9(3), 361–374. https://doi.org/10.1039/c2mb25408e
  • 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
  • Van Linden, O. P. J., Kooistra, A. J., Leurs, R., De Esch, I. J. P., & De Graaf, C. (2014). KLIFS: A knowledge-based structural database to navigate kinase-ligand interaction space. Journal of Medicinal Chemistry, 57(2), 249–277. https://doi.org/10.1021/jm400378w
  • Wakchaure, P., Velayutham, R., & Roy, K. K. (2019). Structure investigation, enrichment analysis and structure-based repurposing of FDA-approved drugs as inhibitors of BET-BRD4. Journal of Biomolecular Structure & Dynamics, 37(12), 3048–3057. https://doi.org/10.1080/07391102.2018.1507838
  • Wang, R., Chen, Y., Yang, B., Yu, S., Zhao, X., Zhang, C., Hao, C., Zhao, D., & Cheng, M. (2020). Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrrolo[2,3-b]pyridine derivatives as potential anti-tumor agents. Bioorganic Chemistry, 94, 103474. https://doi.org/10.1016/j.bioorg.2019.103474
  • Wei, L., Surma, M., Shi, S., Lambert-Cheatham, N., & Shi, J. (2016). Novel insights into the roles of Rho kinase in cancer. Archivum Immunologiae et Therapiae Experimentalis, 64(4), 259–278. https://doi.org/10.1007/s00005-015-0382-6
  • Wishart, D. S., Feunang, Y. D., Guo, A. C., Lo, E. J., Marcu, A., Grant, J. R., Sajed, T., Johnson, D., Li, C., Sayeeda, Z., Assempour, N., Iynkkaran, I., Liu, Y., Maciejewski, A., Gale, N., Wilson, A., Chin, L., Cummings, R., Le, D., … Wilson, M. (2018). DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Research, 46(D1), D1074–D1082. https://doi.org/10.1093/nar/gkx1037

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.