21
Chapter 2
Structure, Thermodynamics and Energetics
of Drug-DNA Interactions: Computer Modeling
and Experiment
Maxim P. Evstigneev and Anna V. Shestopalova
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_2
M. P. Evstigneev ()
Sevastopol National Technical University (SevNTU), Universitetskaya Str., 33,
Sevastopol 99053, Ukraine
e-mail: max_evstigneev@mail.ru
A. V. Shestopalova
A.Usikov Institute for Radiophysics and Electronics National Academy of Sciences of Ukraine
(IRE NASU), Ak. Proskura str., 12, Kharkov 61085, Ukraine
e-mail: shestop@ire.kharkov.ua
Abstract In this chapter we demonstrate the large usefulness of using complex
approach for understanding the mechanism of binding of biologically active compounds (antitumour antibiotics, mutagens etc.) with nucleic acids (NA). The applications of various biophysical methods and computer modeling to determination
of structural (Infra-red and Raman vibrational spectroscopies, computer modeling
by means of Monte-Carlo, molecular docking and molecular dynamics methods)
and thermodynamic (UV-VIS spectrophotometry, microcalorimetry, molecular
dynamics simulation) parameters of NA-ligand complexation with estimation of
the role of water environment in this process, are discussed. The strategy of energy
analysis of the NA-ligand binding reactions in solution is described, which is based
on decomposition of experimentally measured net Gibbs free energy of binding in
terms of separate energetic contributions from particular physical factors. The main
outcome of such analysis is to answer the questions “What physical factors and to
what extent stabilize/destabilize NA-ligand complexes?” and “What physical factors most strongly affect the bioreceptor binding affinity?”
Chapter 2
Structure, Thermodynamics and Energetics
of Drug-DNA Interactions: Computer Modeling
and Experiment
Maxim P. Evstigneev and Anna V. Shestopalova
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_2
M. P. Evstigneev ()
Sevastopol National Technical University (SevNTU), Universitetskaya Str., 33,
Sevastopol 99053, Ukraine
e-mail: max_evstigneev@mail.ru
A. V. Shestopalova
A.Usikov Institute for Radiophysics and Electronics National Academy of Sciences of Ukraine
(IRE NASU), Ak. Proskura str., 12, Kharkov 61085, Ukraine
e-mail: shestop@ire.kharkov.ua
Abstract In this chapter we demonstrate the large usefulness of using complex
approach for understanding the mechanism of binding of biologically active compounds (antitumour antibiotics, mutagens etc.) with nucleic acids (NA). The applications of various biophysical methods and computer modeling to determination
of structural (Infra-red and Raman vibrational spectroscopies, computer modeling
by means of Monte-Carlo, molecular docking and molecular dynamics methods)
and thermodynamic (UV-VIS spectrophotometry, microcalorimetry, molecular
dynamics simulation) parameters of NA-ligand complexation with estimation of
the role of water environment in this process, are discussed. The strategy of energy
analysis of the NA-ligand binding reactions in solution is described, which is based
on decomposition of experimentally measured net Gibbs free energy of binding in
terms of separate energetic contributions from particular physical factors. The main
outcome of such analysis is to answer the questions “What physical factors and to
what extent stabilize/destabilize NA-ligand complexes?” and “What physical factors most strongly affect the bioreceptor binding affinity?”