Document Type : Full research article
Author
Department of Chemistry, Payame Noor University, 19395-4697 Tehran, Iran
Abstract
The interactions of 6twk protein with Ectoine drug, Polyamidoamine (PAMAM) /Ectoine and histidine modified PAMAM/Ectoine were investigated using molecular docking and molecular dynamics simulation. Based on the results of molecular docking increasing of binding energy and the decreasing of inhibition constant of the compounds, increase their inhibitory activity. Protein stability in complex with these ligands was investigated using molecular dynamics simulation approach. Results molecular dynamics simulation displayed that histidine modified PAMAM/Ectoine with the lowest mean square displacement (MSD) is the better suitable to deliver the ectoine drug. This causes the most controlled/diffusion of ectoine drug molecule. So, histidine modified PAMAM/Ectoine conjugate can be introduced for further investigations on interaction of ectoine drug and 6twk protein.
Keywords
[1] L. Nair, S. Jagadeeshan, S.A. Nair and G.V. Kumar, Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier PLGA, Int. J. Nanomedicine 6 (2011) 1685-1697.
[2] A. Rengaraj, P. Puthiaraj, Y. Haldorai, N.S. Heo, S.K. Hwang, Y.K. Han, S. Kwon, W.S. Ahn and Y.S. Huh, Porous Covalent Triazine Polymer as a Potential Nanocargo for Cancer Therapy and Imaging, ACS Appl. Mater. Interfaces 8 (2016) 8947–8955.
[3] K. Ariga, K. Kawakami, M. Ebara, Y. Kotsuchibashi, Q. Ji and J.P. Hill, Bioinspired nanoarchitectonics as emerging drug delivery systems, New J. Chem. 38 (2014) 5149–5163.
[4] U. Boas and P.M. Heegaard, Dendrimers in drug research, Chem. Soc. Rev. 33 (2004) 43–63.
[5] C. Dufes, I.F. Uchegbu and A.G. Schatzlein, Dendrimers in gene delivery, Adv. Drug Delivery Rev. 57 (2005) 2177–2202.
[6] Y. Cheng, Z. Xu, M. Ma and T. Xu, Dendrimers as drug carriers: applications in different routes of drug administration, J. Pharm. Sci. 97 (2008) 123–143.
[7] S. Sadekar and H. Ghandehari, Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery, Adv. Drug Delivery Rev. 64 (2012) 571–588.
[8] C. Pan, C. Kumar, S. Bohl, U. Klingmueller and M. Mann, Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions, Mol. Cell. Proteomics 8 (2009) 443–450.
[9] X. Zhang, Y. Zeng, T. Yu, J. Chen, G. Yang and Y. Li, Tetrathiafulvalene terminal-decorated PAMAM dendrimers for triggered release synergistically stimulated by redox and CB, Langmuir 30 (2014) 718–726.
[10] F. Aulenta, W. Hayes and S. Rannard, Dendrimers: a new class of nanoscopic containers and delivery devices, Eur. Pol. J. 39 (2003) 1741-1771.
[11] S.Y. Wu, H.Y. Chou, H.C. Tsai, R. Anbazhagan, C.H. Yuh, J. M.Yang and Y.H. Chang, Amino acid-modified PAMAM dendritic nanocarriers as effective chemotherapeutic d rug vehicles in cancer treatment: a study using zebrafish as a cancer model, RSC Adv. 10 (2020) 20682- 20690.
[12] M. Sheikhpour, A. Sadeghi, F. Yazdian, A. Movafagh and A. Mansoori, Anticancer and apoptotic effects of ectoine and hydroxyectoine on non-small cell lung cancer cells: An in-vitro investigation, Multidiscipl. Cancer Invest. 3 (2019) 14-20.
[13] J.M. Pastor, M. Salvador, M. Argandona, V. Bernal, M. Reina-Bueno, L.N. Csonka, J.L. Iborra, C. Vargas, J.J. Nieto and M. Canovas, Ectoines in cell stress protection: Uses and biotechnological production, Biotechnol. Adv. 28 (2010) 782–801.
[14] M.B. Hahn, S. Meyer, M.A. Schroter, H. J. Kunte,T. Solomun and H. Sturm, DNA protection by ectoine from ionizing radiation Molecular mechanisms. Phys. Chem. Chem. Phys. 19 (2017) 25717–25722.
[15] R. Dias and W. Filgueira de Azevedo Jr, Molecular docking algorithms, Curr. Drug Targets 9 (2008) 1040-1047.
[16] A. Rengaraj, B. Subbiah, Y. Haldorai, D. Yesudhas, H.J. Yun, S. Kwon, S. Choi, Y.K. Han, E.S. Kim, H. Shenpagam and Y.S. Huh, PAMAM/5-fluorouracil drug conjugate for targeting E6 and E7 oncoproteins in cervical cancer: a combined experimental/in silico approach, RSC Adv. 7(2017) 5046-5054.
[17] Z. Shariatinia, A. Mazloom Jalali and F. Afshar Taromi, Molecular dynamics simulations on desulfurization of n-octane/thiophene mixture using silica filled polydimethylsiloxane nanocomposite membranes, 24 (2016) Model Simul. Mater. Sci. Eng. 035002- 035011.
[18] A. Mazloom Jalali, Z. Shariatinia and F. Afshar Taromi, Desulfurization efficiency of polydimethylsiloxane/silica nanoparticle nanocomposite membranes: MD simulations, Comput. Mater Sci. 139 (2017) 115–124.
[19] S. Salar, F. Mehrnejad, R.H. Sajedi and J. Mohammadnejad Arough, Chitosan nanoparticles-trypsin interactions: biophysicochemical and molecular dynamics simulation studies, Int. J. Biol. Macromol. 103 (2017) 902–909.
[20] M. Yahyaei, F. Mehrnejad, H. Naderi-manesh and A.H. Rezayan, Follicle-stimulating hormone encapsulation in the cholesterolmodified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations, Eur. J. Pharm. Sci. 107(2017) 126–137.
[21] G. Morris and R. Huey, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J. Comput. Chem. 30(2009) 2785-2791.
[22] H. Sun, COMPASS: an ab initio force-field optimized for condensed-phase applications overview with details on alkane and benzene compounds, J. Phys. Chem. B 102(1998) 7338–7364.
[23] D.P. Otto and M.M. de Villiers, All-atomistic molecular dynamics (AA-MD) studies and pharmacokinetic performance of PAMAM-dendrimer-furosemide delivery systems, Int. J. Pharm. 547(2018) 545–555.
[24] X.D. Guo, J.P.K. Tan, S.H. Kim, L.J. Zhang, Y. Zhang, J.L. Hedrick, Y.Y. Yang and Y. Qian, Computational studies on self-assembled paclitaxel structures: templates for hierarchical block copolymer assemblies and sustained drug release, Biomaterials 30 (2009) 6556–6563.
[25] M.M. Mirhosseini, M. Rahmati, S.S. Zargarian and R. Khordad, Molecular dynamics simulation of functionalized graphene surface for high efficient loading of doxorubicin, J. Mol. Struct. 1141(2017) 441–450.
[26] Accelrys Software Inc., San Diego, (2017).
[27] K. Sargsyan, C. Grauffel and C. Lim, How molecular size impacts RMSD applications in molecular dynamics simulations, J. Chem. Theory Comput. 13(2017) 1518−1524.
[28] Y. Liu, V.S. Bryantsev and M.S. Diallo, et al., PAMAM dendrimers undergo pH responsive conformational changes without swelling, J. Am. Chem. Soc. 131 (2009) 2798–2799.
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