The effective model of the human Acetyl-CoA Carboxylase inhibition by aromatic-structure inhibitors
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The research investigates the inhibition of fatty acid biosynthesis of the human Acetyl-CoA Carboxylaseenzyme 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 ofcardiovascular risk factors increasing the incidence of coronary heart disease and type-2 diabetes. Theeffective interoperability between ligand and enzyme is characterized by a 50% concentration of enzymeinhibitor (IC50) which was determined by experiment, and the factor of geometry structure of the ligands whichare 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 usingHyperChem 8.0.10 and Padel Descriptor 2.21 softwares. The result data are processed with the combination ofclassical statistical methods and modern bioinformatics methods using the statistical softwares of Departmentof Pharmaceutical Technology – Jadavpur University – India and R v3.3.1 software in order to accomplish amodel of the quantitative structure - activity relationship between aromatic-structure ligands inhibiting fattyacid biosynthesis of the human Acetyl-CoA Carboxylase.
Abstract
The research investigates the inhibition of fatty acid biosynthesis of the human Acetyl-CoA Carboxylaseenzyme 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 ofcardiovascular risk factors increasing the incidence of coronary heart disease and type-2 diabetes. Theeffective interoperability between ligand and enzyme is characterized by a 50% concentration of enzymeinhibitor (IC50) which was determined by experiment, and the factor of geometry structure of the ligands whichare 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 usingHyperChem 8.0.10 and Padel Descriptor 2.21 softwares. The result data are processed with the combination ofclassical statistical methods and modern bioinformatics methods using the statistical softwares of Departmentof Pharmaceutical Technology – Jadavpur University – India and R v3.3.1 software in order to accomplish amodel of the quantitative structure - activity relationship between aromatic-structure ligands inhibiting fattyacid biosynthesis of the human Acetyl-CoA Carboxylase.
참고문헌 (18)
- T. Q. Than, "Metabolic syndrome", Journal of Cardiology Information, 21(9), pp.1~5 (2004)
- L. X. Truong, "Clinical biochemistry" (2015), Medical Publishers
- Salih J. Wakil, "Fatty acid metabolism: target for metabolic syndrome", Journal of Lipid Research, 50(Supplement), pp.S138~S143 (2009), American Society for Biochemistry & Molecular Biology (ASBMB)[DOI]
- Timothy H. Tran, "Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase", Nature, 518(7537), pp.120~124 (2015), Springer Nature[DOI]
- L. Tong, "Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery", Cellular and Molecular Life Sciences, 62(16), pp.1784~1803 (2005), Springer Nature[DOI]
- "The Binding Database"[URL]
- "PaDEL-Descriptor"[URL]
- Kunal Roy, "Quantitative Structure-Activity Relationships in Drug Design - Predictive Toxicology and Risk Assessment" (2015), Scopus
- "Hypercube, Inc"[URL]
- Warren J. Hehre, "A Guide to Molecular Mechanics and Quantum Chemical Calculations" (2003), Wavefunction
- Pravin Ambure, "“NanoBRIDGES” software: Open access tools to perform QSAR and nano-QSAR modeling", Chemometrics and Intelligent Laboratory Systems, 147, pp.1~13 (2015), Elsevier BV[DOI]
- Melanie Mitchell, "Introduction to Genetic Algorithms" (1999), The MIT Press
- "R : A language and environment for statistical computing"[URL]
- J. Kim, "HyFIS: adaptive neuro-fuzzy inference systems and their application to nonlinear dynamical systems", Neural Networks, 12(9), pp.1301~1319 (1999), Elsevier BV[DOI]
- R. Todeschini, "Handbook of Molecular Descriptors" (2000), Wiley-VCH
- K. Roy, "Introduction of Extended Topochemical Atom (ETA) Indices in the Valence Electron Mobile (VEM) Environment as Tools for QSAR", QSPR Studies, 2003, pp.2, 599~620
- Kunal Roy, "QSTR with Extended Topochemical Atom Indices. 10. Modeling of Toxicity of Organic Chemicals to Humans Using Different Chemometric Tools", Chemical Biology & Drug Design, 72(5), pp.383~394 (2008), Wiley-Blackwell[DOI]
- R. T. Sanderson, "Electronegativity and bond energy", Journal of the American Chemical Society, 105(8), pp.2259~2261 (1983), American Chemical Society (ACS)[DOI]