Connecting the dots in the mechanism of action of Cucurbitacin E (CurE) – path analysis and steered molecular dynamics reveal the precise site of entry and the passage of CurE in filamentous actin

References

• Allingham, J. S., Klenchin, V. A., & Rayment, I. (2006). Actin-targeting natural products: Structures, properties and mechanisms of action. Cellular and Molecular Life Sciences, 63(18), 2119–2134. doi:10.1007/s00018-006-6157-9
   PubMed Web of Science ®Google Scholar
• Anuradha, A., Annadurai, R. S., & Shashidhara, L. S. (2007). Actin cytoskeleton as a putative target of the neem limonoid Azadirachtin A. Insect Biochemistry and Molecular Biology, 37(6), 627–663. doi:10.1016/j.ibmb.2007.03.009
   PubMed Web of Science ®Google Scholar
• Begum Syed, S., Shahbaaz, M., Hassan Khan, S., Srivastava, S., Islam, A., Ahmad, F., & Hassan, I. (2019). Estimation of pH effect on the structure and stability of kinase domain of human integrin-linked kinase. Journal of Biomolecular Structure & Dynamics, 37(1), 156–165. doi:10.1080/07391102.2017.1420492
   PubMed Web of Science ®Google Scholar
• Case, D. A., Darden, T. A., Cheatham, T. E., Simmerling, C. L., Wang, J., Duke, R. E., … Merz, K. M. (2012). AMBER 12. Reference Manual. San Francisco, CA: University of California.
   Google Scholar
• Cheng, Y. M., Shen, C. J., Chang, C. C., Chou, C. Y., Tsai, C. C., & Hsu, Y. C. (2017). Inducement of apoptosis by cucurbitacin E, a tetracyclic triterpenes, through death receptor 5 in human cervical cancer cell lines. Cell Death Discovery, 3, 17014. doi:10.1038/cddiscovery.2017.14
   PubMed Web of Science ®Google Scholar
• Chowdhury, R., & Bajaj, C. (2010). Multi-level grid algorithms for faster molecular energetics, Proceedings of the 14th ACM Symposium on Solid and Physical Modeling - SPM 10, New York, USA, pp. 147–152.
   Google Scholar
• Sadat Mohajer, F., Parvizpour, S., Razmara, J., & Shahir Shamsir, M. (2018). The two mutations of actin–myosin interface and their effect on the dynamics, structures, and functions of skeletal muscle actin. Journal of Biomolecular Structure and Dynamics, 37(2), 1–11. doi:10.1080/07391102.2018.1427630
   PubMed Web of Science ®Google Scholar
• Grubmüller, H., Heymann, B., & Tavan, P. (1996). Ligand binding: Molecular mechanics calculation of the streptavidin-biotin rupture force. Science, 271(5251), 997–999. doi:10.1126/science.271.5251.997
   PubMed Web of Science ®Google Scholar
• Hess, B., Kutzner, C., van der Spoel, D., & Lindah, E. (2008). GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. Journal of Chemical Theory and Computation, 4(3), 435–447. doi:10.1021/ct700301q
   PubMed Web of Science ®Google Scholar
• Holt, P. A., Chaires, J. B., & Trent, J. O. (2008). Molecular docking of intercalators and groove-binders to nucleic acids using autodock and surflex. Journal of Chemical Information and Modeling, 48(8), 1602–1615. doi:10.1021/ci800063v
   PubMed Web of Science ®Google Scholar
• Isralewitz, B., Gao, M., & Schulten, K. (2001). Steered molecular dynamics and mechanical functions of proteins. Current Opinion in Structural Biology, 11 (2), 224–230. doi:10.1016/S0959-440X(00)00194-9
   PubMed Web of Science ®Google Scholar
• Kästner, J. (2011). Umbrella Sampling. Wiley Interdisciplinary Reviews: Computational Molecular Science, 1, 932–942. doi:10.1002/wcms.66
   Web of Science ®Google Scholar
• Korn, E. D. (1982). Actin polymerization and its regulation by proteins from nonmuscle cells. Physiological Reviews, 62(2), 672–737. doi:10.1152/physrev.1982.62.2.672
   PubMed Web of Science ®Google Scholar
• Kumar Pravin, R., Roopa, L., Upendra, N., Mohammed Sudheer, M. M., & Naveen, K. (2016). Docking, molecular dynamics and QM/MM studies to delineate the mode of binding of CucurbitacinE to F-actin. Journal of Molecular Graphics & Modelling, 63, 29–37. doi:10.1016/j.jmgm.2015.11.007
   PubMed Web of Science ®Google Scholar
• Kumari, R., Kumar, R., & Lynn, A. (2014). g_mmpbsa-a GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. doi:10.1021/ci500020m
   PubMed Web of Science ®Google Scholar
• McCammon, J. A., & Harvey, S. (1987). Dynamics of proteins and nucleic acids (pp. 44). Cambridge: Cambridge University Press.
   Google Scholar
• Orzechowski, M., & Cieplak, P. (2005). Application of steered molecular dynamics (SMD) to study DNA–drug complexes and probing helical propensity of amino acids. Journal of Physics, Condensed Matter, 17, 1627–1640.
   Web of Science ®Google Scholar
• Pollard, T. D., Blanchoin, L., & Mullins, R. D. (2000). Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annual Review of Biophysics and Biomolecular Structure, 29(1), 545–576. doi:10.1146/annurev.biophys.29.1.545
   PubMedGoogle Scholar
• Pravin Kumar, R., Manoj, M. N., Kush, A., & Annadurai, R. S. (2007). In silico approach of azadirachtin binding with actins. Insect Biochemistry and Molecular Biology, 37(6), 635–640. doi:10.1016/j.ibmb.2007.03.010
   PubMed Web of Science ®Google Scholar
• Raikhlin-Eisenkraft, B., & Bentur, Y. (2000). Ecbalium elaterium (squirting cucumber) remedy or poison? Journal of Toxicology. Clinical Toxicology, 38(3), 305–308.
   PubMed Web of Science ®Google Scholar
• Salomon-Ferrer, R., Case, D. A., & Walker, R. C. (2013). An overview of the Amber biomolecular simulation package. Wiley Interdisciplinary Reviews: Computational Molecular Science, 3(2), 198–210. doi:10.1002/wcms.1121
   Web of Science ®Google Scholar
• Schmidt, R. K., Teo, B., & Brady, J. W. (1995). Use of umbrella sampling in the calculation of the potential of mean force for maltose in vacuum from molecular dynamics simulations. The Journal of Physical Chemistry, 29, 11339–11343. doi:10.1021/j100029a007
   Google Scholar
• Sheterline, P., Clayton, J., & Sparrow, J. C. (1998). Actin. UK: Oxford University Press.
   Google Scholar
• Sörensen, P. M., Iacob, R. E., Fritzsche, M., Engen, J. R., Brieher, W. M., Charras, G., & Eggert, U. S. (2012). The natural product cucurbitacin E inhibits depolymerization of actin filaments. ACS Chemical Biology, 7(9), 1502–1508. doi:10.1021/cb300254s
   PubMed Web of Science ®Google Scholar
• Spector, I., Braet, F., Shochet, N. R., & Bubb, M. R. (1999). New anti-actin drugs in the study of the organization and function of the actin cytoskeleton. Microscopy Research and Technique, 47(1), 18–37. doi:10.1002/(SICI)1097-0029(19991001)47:1<18::AID-JEMT3>3.0.CO;2-E
   PubMed Web of Science ®Google Scholar
• Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. C. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry, 26(16), 1701–1718. doi:10.1002/jcc.20291
   PubMed Web of Science ®Google Scholar
• Vojtěch, V., & Barbora, K. (2017). Tunnel detection in protein structures using sampling-based motion planning. Robot Motion and Control, 11th International Workshop, 185–192.
   Google Scholar
• Xu, L., Hasin, N., Shen, M., He, J., Xue, Y., Zhou, X., … Jones, G. W. (2013). Using steered molecular dynamics to predict and assess Hsp70 substrate-binding domain mutants that alter prion propagation. In G. Legname ed., PLoS Computational Biology, 9(1), e1002896. doi:10.1371/journal.pcbi.1002896
   Google Scholar
• Zhang, B., Su, Z., Tay, T. E., & Vincent, B. C. T. (2010). Mechanism of CDK5 activation revealed by steered molecular dynamics simulations and energy calculations. Journal of Molecular Modeling, 161, 1159–1168. doi:10.1007/s00894-009-0629-4
   Google Scholar
• Zhang, J., Zheng, Q., & Zhang, H. (2010). Unbinding of glucose from human pulmonary surfactant protein D studied by steered molecular dynamics simulations. Chemical Physics Letters, 484(4–6), 338–343. doi:10.1016/j.cplett.2009.12.022
   Web of Science ®Google Scholar