title: The Complexation of the Anticancer Drug ThioTEPA with Methylated DNA Base Guanine: Combined Ab Initio and QTAIM Investigation.
abstract: Non-covalent complexes of methylated nitrogenous DNA base guanine (m(9) Gua) with 1 to 6 molecules of anticancer drug ThioTEPA (1,1',1''-phosphorothioyltriaziridine) have been investigated by molecular modeling techniques (molecular docking and DFT geometry optimization), ab initio wavefunction calculations and the quantum theory of atoms in molecules (QTAIM). The accuracy of complex structures predicted by standard molecular docking techniques have been assessed by comparing them with ab initio calculations, and the most important differences have been discussed. Obtained stabilization enthalpies (kcal/mol) for the m(9) Gua⋅⋅⋅(ThioTEPA)n complexes with n=1…6 have been found to be -15.6, -26.5, -38.4, -49.6, -60.5 and -69.3 respectively. The non-covalent interactions revealed by the QTAIM method have been shown to be a dominating factor responsible for the complex stability, with hydrogen bonds of NH⋅⋅⋅N type being the most important interactions in small (n=1 to 4) and CH⋅⋅⋅N bonds - in large (n=5, 6) complexes. The obtained results may help to understand ThioTEPA-DNA interactions and clarify the mechanism of the drug action.
authors.affiliation: Faculty of Physics, Taras Shevchenko National University of Kyiv 4, Hlushkova ave., 01601 Kyiv, Ukraine phone/fax: +380974524557. tim_mail@ukr.net.
authors.forename: Tymofii Yu
authors.initials: TY
authors.lastname: Nikolaienko
authors.affiliation: Faculty of Physics, Taras Shevchenko National University of Kyiv 4, Hlushkova ave., 01601 Kyiv, Ukraine phone/fax: +380974524557.
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Bulavin
authors.affiliation: Medical Institute, Sumy State University, Ministry of Education and Science of Ukraine, 2 R. Korsakova Str., 40007 Sumy, Ukraine.
authors.forename: Leonid F
authors.initials: LF
authors.lastname: Sukhodub
keywords: Ab initio calculations; Anticancer drug design; DNA; Hydrogen bonds; Medicinal chemistry