Interaction of DNA nucleotide bases with anticancer drug ThioTEPA: molecular docking and quantum-mechanical analysis

Samtsevich, Artem I.; Булавин, Л. А.; Sukhodub, L. F.; Nikolaienko, Tymofii Yu.

doi:10.15407/ubj86.02.050

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Масс-спектрометрические исследования взаимодействия химиотерапевтических препаратов с компонентами нуклеиновых кислот были продолжены Суходубом Л.Ф. и его учениками в Институте прикладной физики НАН Украины (г. Сумы) [10,35,[45][46][47][48][49][50] и Сумском государственном университете МОН Украины [51,52].…”

Section: взаимодействие алкилирующих противоопухолевых препаратов сunclassified

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

2019

Biophysical Bulletin

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Background: Determination of molecular mechanisms of action of drugs forms a scientific basis for the directed search of efficient medications. Assumed pathways of interactions of chemotherapeutic drugs which affect infectious agents and malignant neoplasm with their potential molecular targets require direct evidences at the molecular level. Such evidences can be obtained by means of molecular biophysics which possesses an arsenal of new powerful physical techniques for studying the intermolecular interactions of biomolecules and pharmaceutical agents. Objectives: The aim of this review is the generalization of the results of long standing investigations on the molecular mechanisms of action of chemotherapeutic agents performed in the biophysical departments of B. Verkin Institute for Low Temperature Physics and Engineering (ILTPE) of the NAS of Ukraine. The first part of the review is devoted to anticancer and antiviral agents targeted presumably at nucleic acids. Materials and methods: Mass spectrometric studies of molecules of thermally unstable drugs and their complexes with biomolecules have been advanced significantly due to the development of soft ionization/desorption techniques; the researchers of ILTPE have made noticeable contribution to this field. The methods of molecular spectroscopy and computer modeling by means of quantum chemistry were applied in the combined investigations. Results: The objects of study were the systems composed of chemotherapeutic drugs – thiophosphamide, phenazine derivatives and phenazine-modified antigene/antisense oligonucleotides, quaternary compounds, tilorone – and their molecular targets – DNA, oligo- and polynucleotides and nucleic acids components. The mechanisms of action of these drugs established at the model molecular level consisted in the specific and nonspecific noncovalent or covalent interactions of the drugs’ molecules with nucleic acids and their components and in the formation of stable drug-target complexes. Conclusions: The experience of investigations conducted during several decades at the ILTPE has demonstrated the efficiency of the application of the methods and approaches of molecular biophysics to establishing of molecular mechanisms of drugs action. The basic results obtained are of practical importance for the further development of new efficient pharmaceuticals.

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Section: взаимодействие алкилирующих противоопухолевых препаратов сunclassified

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

2019

Biophysical Bulletin

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“…The accurate determination of the intermolecular interaction energy is essential for obtaining the reliable results in the physical modeling of molecular systems with such methods as molecular dynamics [1][2][3][4], Monte Carlo [5][6][7], molecular docking [8][9][10] C i t a t i o n: Nikolaienko T.Yu., Bulavin L.A. Approximating electrostatic potential of molecules with point charges mimicking the electron pairs. Ukr.…”

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confidence: 99%

Approximating Electrostatic Potential of Molecules with Point Charges Mimicking the Electron Pairs

Nikolaienko,

Bulavin

2023

Ukr. J. Phys.

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The electrostatic component used in the traditional force fields significantly impacts their accuracy in modelling the noncovalent interactions peculiar to biomolecular systems, including hydrogen bonding. In this contribution, we present a physical model for approximating the electrostatic potential of a molecule (MEP) based on the first-principle decomposition of its charge density distribution into the localized components. In contrast to conventional schemes, which typically use atom-centered charges to approximate MEP, the proposed approach locates such charges in the positions selected so as to mimic the anisotropy of the electron density distributions related to the electron pairs of atoms or covalent bonds. This peculiarity leads to a more accurate representation of the overall electrostatic potential, as verified by applying the proposed model to approximate the electrostatic component of the intermolecular interaction energy in 145 noncovalently bound molecular complexes from GMTKN55 database. This benchmark showed the root-mean-square difference between the true and approximated values of the electrostatic component of 2.7 kcal/mol, which is 2.2 times lower as compared to the traditional RESP charges method used as a baseline.

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Interaction of DNA nucleotide bases with anticancer drug ThioTEPA: molecular docking and quantum-mechanical analysis

Cited by 2 publications

References 21 publications

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

Approximating Electrostatic Potential of Molecules with Point Charges Mimicking the Electron Pairs

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