Study on the Interactions of Two Isomer Selaginellins as Novel Small Molecule Inhibitors Targeting PTP1B by Docking and Molecular Dynamics Simulations

doi:10.4236/oalib.1104277

OALib Journal期刊
ISSN: 2333-9721
费用：99美元

查看量	下载量

Open Access Library Journal 5 2018

查看所有领域

Study on the Interactions of Two Isomer Selaginellins as Novel Small Molecule Inhibitors Targeting PTP1B by Docking and Molecular Dynamics Simulations

DOI: 10.4236/oalib.1104277, PP. 1-12

Li Wang, Yi Wang, Dan Meng, Honglei Li

Subject Areas: Pharmacology, Drugs & Devices

Keywords: PTP1B, Molecular Docking, Selaginellins, Molecular Dynamics Simulations

Full-Text Cite this paper Add to My Lib

Abstract

Protein Tyrosine Phosphatase 1B (PTP1B) plays a key role in down-regulation of insulin and leptin signaling pathways. Therefore, development of novel inhibitors of PTP1B has becoming research focus in reducing blood sugar levels for Diabetes Mellitus and Obesity. Hence, we selected two isomer Selaginellins (1 and 2) to explain and analyze the binding mechanism of the two potential inhibitors against the PTP1B by molecule docking and molecular dynamics simulations. Firstly, the two isomers (1 and 2) and the initial ligand 19 were docked to the receptor of PTP1B by using molecular docking technology. Secondly, taken the 19 as an indicator, molecular dynamic (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) methods were requested to assess the binding affinity and complex stability of the two chemicals towards PTP1B. Finally, we explained that the interactions of compound 1 and 2 take up the active binding site PTP1B. Simultaneously, energy decomposition analysis recognized several amino acid residues situated in substrate-binding site that might provide clues for future inhibitor exploitation towards PTP1B. In conclusion, these results may explain the reasons of differences of optical isomer biological activity and provide valuable information for developing novel inhibitors targeting PTP1B-mediated glucose transport and metabolism for Diabetes Mellitus and Obesity therapeutics.

Cite this paper

Wang, L. , Wang, Y. , Meng, D. and Li, H. (2018). Study on the Interactions of Two Isomer Selaginellins as Novel Small Molecule Inhibitors Targeting PTP1B by Docking and Molecular Dynamics Simulations. Open Access Library Journal, 5, e4277. doi: http://dx.doi.org/10.4236/oalib.1104277.

References

[1]	Asante-Appiah, E. and Kennedy, B.P. (2003) Protein Tyrosine Phosphatases: The Quest for Negative Regulators of Insulin Action. American Journal of Physiology Endocrinology and Metabolism, 284, E663-E670. https://doi.org/10.1152/ajpendo.00462.2002
[2]	Lund, I.K., Hansen, J.A., Andersen, H.S., Moller, N.P.H. and Billestrup, N. (2005) Mechanism of Protein Tyrosine Phosphatase 1B-Mediated Inhibition of Leptin Signalling. Journal of Molecular Endocrinology, 34, 339-351. https://doi.org/10.1677/jme.1.01694
[3]	Tonks, N.K. and Neel, B.G. (2001) Combinatorial Control of the Specificity of Protein Tyrosine Phosphatases. Current Opinion in Cell Biology, 13, 182-195. https://doi.org/10.1016/S0955-0674(00)00196-4
[4]	Blume-Jensen, P. and Hunter, T. (2001) Oncogenic Kinase Signaling. Nature, 411, 355-365. https://doi.org/10.1038/35077225
[5]	Thareja, S., Aggarwal, S., Bhardwaj, T.R. and Kumar, M. (2012) Protein Tyrosine Phosphatase 1B Inhibitors: A Molecular Level Legitimate Approach for the Management of Diabetes Mellitus. Med Res Rev., 32, 459-517. https://doi.org/10.1002/med.20219
[6]	Zhang, Z.Y. (2002) Protein Tyrosine Phosphatases: Structure and Function, Substrate Specificity, and Inhibitor Development. Annual Review of Pharmacology and Toxicology, 42, 209-234. https://doi.org/10.1146/annurev.pharmtox.42.083001.144616
[7]	Lau, C.K., Bayly, C.I., Gauthier, J.Y., Li, C.S., Therien, M., Asante-Appiah, E., Cromlish, W., Boie, Y., Forghani, F., Desmarais, S., Wang, Q., Skorey, K., Waddleton, D., Payette, P., Rama-chandran, C., Kennedy, B.P. and Scapin, G. (2004) Structure Based Design of a Series of Potent and Selective Non Peptidic PTP-1B Inhibitors. Bioorganic & Medicinal Chemistry Letters, 14, 1043-1048. https://doi.org/10.1016/j.bmcl.2003.11.076
[8]	Dufresne, C., Roy, P., Wang, Z., Asante-Appiah, E., Cromlish, W., Boie, Y., Forghani, F., Desmarais, S., Wang, Q., Skorey, K., Waddleton, D., Ramachandran, C., Kennedy, B.P., Xu, L., Gordon, R., Chan, C.C. and Leblanc, Y. (2004) The Development of Potent Non-Peptidic PTP-1B Inhibitors. Bioorganic & Medicinal Chemistry Letters, 14, 1039-1042. https://doi.org/10.1016/j.bmcl.2003.11.048
[9]	Zheng, X.K., Zhang, L., Wang, W.W., Wu, Y.Y., Zhang, Q.B. and Feng, W.S. (2011) Anti-Diabetic Activity and Potential Mechanism of Total Flavonoids of Selaginella tamariscina (Beauv.) Spring in Rats Induced by High Fat Diet and Low Dose STZ. Journal of Ethnopharmacology, 137, 662-668. https://doi.org/10.1016/j.jep.2011.06.018
[10]	Zheng, X.K., Wang, W.W., Zhang, L., Su, C.F., Wu, Y.Y., Ke, Y.Y., Hou, Q.W., Liu, Z.Y., Gao, A.S. and Feng, W.S. (2013) Antihyperlipidaemic and Antioxidant Effect of the Total Flavonoids in Selaginella tamariscina (Beauv.) Spring in Diabetic Mice. J Pharm Pharmacol., 65, 757-766. https://doi.org/10.1111/jphp.12035
[11]	Nguyen, P.H., Zhao, B.T., Ali, M.Y., Choi, J.S., Rhyu, D.Y., Min, B.S. and Woo, M.H. (2015) Insulin-Mimetic Selaginellins from Selaginella tamariscina with Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity. Journal of Natural Products, 78, 34-42. https://doi.org/10.1021/np5005856
[12]	Lu, Q., Cai, Z., Fu, J., Luo, S., Liu, C., Li, X. and Zhao, D. (2014) Molecular Docking and Molecular Dynamics Studies on the Interactions of Hydroxylated Polybro-minated Diphenyl Ethers to Estrogen Receptor Alpha. Ecotoxicology and Environmental Safety, 101, 83-89. https://doi.org/10.1016/j.ecoenv.2013.12.018
[13]	Podder, A., Pandey, D. and Latha, N. (2016) Investigating the Structural Impact of S311C Mutation in DRD2 Receptor by Molecular Dynamics & Docking Studies. Biochimie, 123, 52-64. https://doi.org/10.1016/j.biochi.2016.01.011
[14]	Selvam, C., Jachak, S.M., Thilagavathi, R. and Chakraborti ,A.K. (2005) Design, Synthesis, Biological Evaluation and Molecular Docking of Curcumin Analogues as Antioxidant, Cyclooxygenase Inhibitory and Anti-Inflammatory Agents. Bioorganic & Medicinal Chemistry Letters, 15, 1793-1797. https://doi.org/10.1016/j.bmcl.2005.02.039
[15]	Qin, H.-L., Shang, Z.-P., Jantan, I., Tan, O.U., Hussain, M.A., Sher, M. and Bukhari, S.N.A. (2015) Molecular Docking Studies and Biological Evaluation of Chalcone Based Pyrazolines as Tyrosinase Inhibitors and Potential Anticancer Agents. RSC Advances, 5, 46330-46338. https://doi.org/10.1039/C5RA02995C
[16]	Zhou, R., Berne, B.J. and Germain, R. (2001) The Free Energy Landscape for β Hairpin Folding in Explicit Water. Proceedings of the National Academy of Sciences of the United States of America, 98, 14931-14936. https://doi.org/10.1073/pnas.201543998
[17]	Wan, Z.N., Li, X., Sun, R., Li, Y.Y., Wang, X.Y., Li, X.R., Rong, L., Shi, Z. and Bao, J.L. (2015) Computer-Assisted Identification of Novel Small Molecule Inhibitors Targeting GLUT1. Journal of Molecular Structure, 1101, 57-65. https://doi.org/10.1016/j.molstruc.2015.07.074
[18]	Reddy, M.V.V.V.S., Ghadiyaram, C., Panigrahi, S.K., Krishnamurthy, N.R., Hosahalli, S., Chandrasekharappa, A.P., Manna, D., Badiger, S.E., Dubey, P.K. and Mangamoori, L.N. (2014) X-Ray Structure of PTP1B in Complex with a New PTP1B Inhibitor. Protein & Peptide Letters, 21, 90-93. https://doi.org/10.2174/09298665113209990089
[19]	Ma, S., Zeng, G., Fang, D., Wang, J., Wu, W., Xie, W., Tan, S. and Zheng, K. (2015) Studies of N9-Arenthenyl Purines as Novel DFG-In and DFG-Out Dual Src/Abl Inhibitors Using 3D-QSAR, Docking and Molecular Dynamics Simulations. Molecular BioSystems, 11, 394-406. https://doi.org/10.1039/C4MB00350K
[20]	Jain, A.N. (2007) Surflex-Dock 2.1: Robust Performance from Ligand Energetic Modeling, Ring Flexibility, and Knowledge-Based Search. Journal of Computer-Aided Molecular Design, 21, 281-306. https://doi.org/10.1007/s10822-007-9114-2
[21]	Bertran, O., Zhang, B., Schlueter, A.D., Halperin, A., Kroeger, M. and Aleman, C. (2013) Computer Simulation of Dendronized Polymers: Organization and Characterization at the Atomistic Level. RSC Advances, 3, 126-140. https://doi.org/10.1039/C2RA22034B
[22]	Salomon-Ferrer, R., Case, D.A. and Walker, R.C. (2013) Previous Article in Issue: State-Specific Multireference Coupled-Cluster Theory. Wiley Interdisciplinary Reviews: Computational Molecular Science, 3, 198-210. https://doi.org/10.1002/wcms.1121
[23]	Batcho, P.F., Case, D.A. and Schlick, T. (2001) Optimized Particle-Mesh Ewald/ Multiple-Time Step Integration for Molecular Dynamics Simulations. The Journal of Chemical Physics, 115, 4003-4018. https://doi.org/10.1063/1.1389854
[24]	Kollman, P.A., Massova, I., Reyes, C., Kuhn, B., Huo, S.H., Chong, L., Lee, M., Lee, T., Duan, Y., Wang, W., Donini, O., Cieplak, P., Srinivasan, J., Case, D.A. and Cheatham, T.E. (2000) Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models. Accounts of Chemical Research, 33, 889-897. https://doi.org/10.1021/ar000033j
[25]	Mhlongo, N.N. and Soliman, M.E.S. (2015) Single H5N1 Influenza A Neuraminidase Mutation Develops Resistance to Oseltamivir Due to Distorted Conformational and Drug Binding Landscape: Multiple Molecular Dynamics Analyses. RSC Advances, 5, 10849-10861. https://doi.org/10.1039/C4RA13494J
[26]	Hayes, J.M., Skamnaki, V.T., Archontis, G., Lamprakis, C., Sarrou, J., Bischler, N., Skaltsounis, A.-L., Zographos, S.E. and Oikonomakos, N.G. (2011) Kinetics, in Silico Docking, Molecular Dynamics, and MM-GBSA Binding Studies on Prototype Indirubins, KT5720, and Staurosporine as Phosphorylase Kinase ATP-Binding Site Inhibitors: The Role of Water Molecules Examined. Proteins, 79, 703-719. https://doi.org/10.1002/prot.22890
[27]	Roe, D.R., Okur, A., Wickstrom, L., Hornak, V. and Simmerling, C. (2007) Secondary Structure Bias in Generalized Born Solvent Models: Comparison of Conformational Ensembles and Free Energy of Solvent Polarization from Explicit and Implicit Solvation. The Journal of Physical Chemistry B, 111, 1846-1857. https://doi.org/10.1021/jp066831u

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133

WeChat 1538708413