Understanding of the conformational flexibility and electrostatic properties of coumarin derivatives in the active site of S. cerevisiae α-glucosidase
- 46 Downloads
This study has been carried out to understand the nature of conformational flexibility and electrostatic properties of polyhydroxyl coumarins derivatives. When these compounds present in the active site of S. cerevisiae α-glucosidase, the lactone rings of the molecules are flanking out, while all benzene rings are embedded deep inside the binding cavity. These hydroxyl groups can interact with the surrounding amino acids by hydrogen bonds easily. When the hydroxyl groups at the C9 of benzene ring are replaced by methoxy groups, there is no evident influence on the hydrogen bonding interactions with the surrounding amino acid Asp68 and Lys155. However, their Laplacian values of electron densities of hydroxyl O–H bonds are obviously decreased in the active site, which suggests concentrated electron densities. In general, most of the electron densities of chemical bonds become more depleted after docking with the S. cerevisiae α-glucosidase, implying strong interactions with the surrounding amino acids. For polyhydroxyl coumarin derivatives, the global maximum values of the molecular electrostatic potential on molecular vdW surfaces stem from hydrogen atoms of the hydroxyl groups. However, the values are decreased evidently and stem from the different atoms in both phases while methoxy group is introduced. These fine details at electronic level allow to better understand the exact interactions between natural coumarins derivatives and target protein.
KeywordsMolecular docking Quantum chemical calculations Molecular electrostatic potential α-glucosidase Charge density distribution
This work was supported by the Fundamental Research Funds for the Central Universities (31920170007) and the Innovative Training Program for College Students (201710742084).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Bader RFW (1990) Atoms in molecules: a quantum theory. Oxford University Press, OxfordGoogle Scholar
- Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision E.01 (2009) Gaussian, Inc. Wallingford CTGoogle Scholar
- Li H, Yao Y, Li L (2017) Coumarins as potential antidiabetic agents. J Pharm Pharmacol. (Epub ahead of print)Google Scholar
- Mary YS, Panicker CY, Thiemann T, Al-Azani M, Al-Saadi AA, Van Alsenoy C, Raju K, War JA, Srivastava SK (2015) Molecular conformational analysis, vibrational spectra, NBO, NLO analysis and molecular docking study of bis [(E)-anthranyl-9-acrylic] anhydride based on density functional theory calculations. Spectrochim Acta A 151:350–359CrossRefGoogle Scholar
- Murray JS, Politzer P (1998) Electrostatic potentials: chemical applications. In: Schleyer PvR (ed) Encyclopedia of computational chemistry. Wiley, West Sussex, p 912–920Google Scholar
- Murray JS, Politzer P (2011) The electrostatic potential: an overview. Wiley Interdiscip Rev 1:153–163Google Scholar
- Singh RN, Baboo V, Rawat P, Kumar A, Verma D (2012) Molecular structure, spectral studies, intra and intermolecular interactions analyzes in a novel ethyl 4-[3-(2-chloro-phenyl)-acryloyl]- 3,5-dimethyl-1H-pyrrole-2-carboxylate and its dimer: A combined DFT and AIM approach. Spectrochim Acta A 94:288–301CrossRefGoogle Scholar