Journal of IKEEE (전기전자학회논문지)

Institute of Korean Electrical and Electronics Engineers (한국전기전자학회)
권호 표지
DOI QR코드

DOI QR Code

The effective model of the human Acetyl-CoA Carboxylase inhibition by aromatic-structure inhibitors

  • Received : 2017.06.13
  • Accepted : 2017.08.30
  • Published : 2017.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

The research investigates the inhibition of fatty acid biosynthesis of the human Acetyl-CoA Carboxylase enzyme by the aromatic-structure inhibitors (also known as ligands) containing variables of substituents, contributing an important role in the treatment of fatty-acid metabolic syndrome expressed by the group of cardiovascular risk factors increasing the incidence of coronary heart disease and type-2 diabetes. The effective interoperability between ligand and enzyme is characterized by a 50% concentration of enzyme inhibitor ($IC_{50}$) which was determined by experiment, and the factor of geometry structure of the ligands which are modeled by quantum mechanical methods using HyperChem 8.0.10 and Gaussian 09W softwares, combining with the calculation of quantum chemical and chemico-physical structural parameters using HyperChem 8.0.10 and Padel Descriptor 2.21 softwares. The result data are processed with the combination of classical statistical methods and modern bioinformatics methods using the statistical softwares of Department of Pharmaceutical Technology - Jadavpur University - India and R v3.3.1 software in order to accomplish a model of the quantitative structure - activity relationship between aromatic-structure ligands inhibiting fatty acid biosynthesis of the human Acetyl-CoA Carboxylase.

Keywords

References

  1. T. Q. Than, " Metabolic syndrome", Journal of Cardiology Information, vol.21, no.9, pp. 1-5, 2004.
  2. L. X. Truong, Clinical biochemistry, 1st ed. Medical Publishers - HoChiMinh City Branch, 2015.
  3. Salih J. Wakil and Lutfi A. Abu-Elheiga, "Fatty acid metabolism: target for metabolic syndrome", Journal of Lipid Research, vol.50, pp. 138-143, 2009. DOI : 10.1194/jlr.R800079-JLR200
  4. Timothy H. Tran and Yu-Shan Hsiao, "Structure and function of a single-chain, multidomain long-chain acyl-CoA carboxylase", Nature, vol.518, pp. 120-124, 2015. DOI : 10.1038/nature13912
  5. Tong L, "Acetyl-coenzyme A carboxylase : crucial metabolic enzyme and attractive target for drug discovery", Cellular and Molecular Life Sciences, vol.62, pp. 1784-1803, 2005. DOI : https://doi.org/10.1007/s00018-005-5121-4
  6. Tiquing Liu, "The Binding Database", http://bindingdb.org/ (URL).
  7. Chun Wei, "PaDEL-Descriptor", http://yapcwsoft.com/dd/padeldescriptor/ (URL).
  8. Kunal Roy, Quantitative Structure-Activity Relationships in Drug Design - Predictive Toxicology and Risk Assessment, 3rd. ed. Scopus, 2015.
  9. MakoLab, "Hypercube, Inc." , http://hyper.com/ (URL).
  10. Warren J. Hehre, A Guide to Molecular Mechanics and Quantum Chemical Calculations, 2nd ed. Wavefunction, 2003.
  11. Ambure and Aher, " NanoBRIDGES software : Open access tools to perform QSAR and nano-QSAR modeling", Chemometrics and Intelligent Laboratory Systems, vol.147, pp. 1-13, 2015. DOI : https://doi.org/10.1016/j.chemolab.2015.07.007
  12. Melanie Mitchell, Introduction to Genetic Algorithms, 5th ed. The MIT Press, 1999.
  13. R Core Team, "R : A language and environment for statistical computing", http://www.R-project.org/ (URL).
  14. J. Kim and N. Kasabov, "HyFIS: adaptive neuro-fuzzy inference systems and their application to nonlinear dynamical systems", Neural Networks, vol.12, pp. 1301-1319, 1999. DOI : https://doi.org/10.1016/S0893-6080(99)00067-2
  15. R. Todeschini and V. Consonni, Handbook of Molecular Descriptors, 1st ed. Wiley-VCH, 2000.
  16. K. Roy and G. Ghosh, "Introduction of Extended Topochemical Atom (ETA) Indices in the Valence Electron Mobile (VEM) Environment as Tools for QSAR/QSPR Studies", Internet Electronic Journal of Molecular Design, vol.2, pp. 599-620, 2003.
  17. K. Roy and G. Ghosh, "QSTR with Extended Topochemical Atom Indices. 10. Modeling of Toxicity of Organic Chemicals to Humans Using Different Chemometric Tools", Chem Biol Drug Des, vol.72, pp. 383-394, 2008. DOI: 10.1111/j.1747-0285.2008.00712.x
  18. R.T. Sanderson, "Electronegativity and Bond Energy", J. Am. Chem. Soc., vol.105, pp. 2259-2261, 1981. DOI : 10.1021/ja00346a026