DEVELOPMENT OF METHODS OF SIMULATION OF THE INTERACTION OF BIOLOGICALLY ACTIVE SUBSTANCES WITH THE ACTIVE CENTER OF ANGIOTENSIN-CONVERTING ENZYME


Cite item

Full Text

Abstract

Nowadays cardiovascular diseases are the main cause of death among the population around the word. The development of new drugs, giving a possibility to normalize blood pressure, is a promising direction in the field of pharmacy and medicine. Now inhibitors of angiotensinconverting enzyme (ACE) are widely adopted for the treatment of hypertension and chronic heart failure. The principle of action of ACE inhibitors is based on blocking the conversion of angiotensin I into angiotensin II, which mediates vasodilation.The aim of the work is a selection of methods of lisinopril interaction with the active center of angiotensin-converting enzyme by molecular dynamics methods.Materials and methods. Lisinopril molecule was used as a ligand; the charges of that ligand were calculated with the density functional theory (DFT) and ub3lyp method with the basis sets 6-31G* and 6-311G**. Simulation of 75 ns of molecular dynamics of lisinopril interaction with the active center of ACE was carried out in the Bioevrica program. As a result of molecular dynamics simulation, the trajectory of the “lisinopril-ACE” system was obtained. After that a comparison of ligand conformations at different points in simulation time with the experimental conformation of the value of standard deviation of coordinates of atoms was made.Results and discussion.The results of simulation have showed that lisinopril with the charges corresponding to basis set 6-311G** behaves consistent with the x-ray data in the active center of the ACE, in contrast to lisinopril with the charges calculated by basis set 6-31G*.Conclusion. The methods of lisinopril interaction modeling with the active center of angiotensin-converting enzyme has been selected. The obtained technique can be used for studying the interaction of substances, similar in structure to lisinopril with the active center of the enzyme (ACE).

About the authors

A. A. Glushko

Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University

Email: alexander.glushko@lcmmp.ru

A. S. Chiriapkin

Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University

Email: alexxx704@yandex.ru

V. S. Chiriapkin

Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University

Email: chiryapkin.v@yandex.ru

A. M. Murtuzalieva

Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University

Email: a.murtuzalieva98@mail.ru

Yu. A. Polkovnikova

Federal State Budget Educational Institution of Higher Education “Voronezh State University”

Email: juli-polk@mail.ru

References

  1. Hilal-Dandan R. Renin and Angiotensin. Chapter 26 in the book “Goodman & Gilman’s”. The pharmacological basis of therapeutics (12th ed.) / edited by Laurence L. Brunton, John S. Lazo, Keith L. Parker. New York: McGraw-Hill, 2006. P. 721–744.
  2. Bangalore S., Fakheri R., Wandel S., Toklu B., Wandel J., Messerli F.H. Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials // BMJ (Clinical research ed.). 2017. N. 356. URL: http://www.bmj.com/content/356/bmj.j4 (дата обращения: 03.10.2017). doi: 10.1136/bmj.j4
  3. Shafi S. Role of ace inhibitors in atherosclerosis. International journal of biomedical and advance research. 2013. N. 12. P. 849–854.
  4. Jandeleit-Dahm K., Cooper M.E. Hypertension and diabetes: role of the renin-angiotensin system // Endocrinol. Metab. Clin. North Am. 2006. N. 35 (3). P. 469–490. doi: 10.1016/j.ecl.2006.06.007
  5. Преображенский Д.В., Некрасова Н.И., Талызина И.В., Патарая С.А., Бугримова М.А. Лизиноприл – гидрофильный ингибитор ангиотензинпревращающего фермента длительного действия: особенности клинической фармакологии и диапазон клинического применения // РМЖ. 2010. №10. С. 684.
  6. Mollica L., Theret I., Antoine M., Perron-Sierra F., Charton Y., Fourquez J.-M., Wierzbicki M., Boutin J.A., Ferry G., Decherchi S., Bottegoni G., Ducrot P., Cavalli A. Molecular dynamics simulations and kinetic measurements to estimate and predict protein−ligand residence times // J. Med. Chem. 2016. N. 59 (15). P. 7167–7176. doi: 10.1021/acs.jmedchem.6b00632
  7. Sharma R., Dhingra N., Patil S. CoMFA, CoMSIA, HQSAR and molecular docking analysis of ionone-based chalcone derivatives as antiprostate cancer activity // Indian J. Pharm. Sci. 2016. N. 78(1). P. 54–64.
  8. Гарсиа-Джакас С.Р., Авдеенко T.В. Мультисерверный подход к высокопроизводительному вычислению молекулярных дескрипторов // Научный вестник НГТУ. 2015. № 1. С. 148–160. doi: 10.17212/1814-1196-2015-1-148-160
  9. Глушко А.А., Воронков А.В., Кодониди И.П., Бичеров А.В., Черников М.В. Молекулярный докинг N-замещенного производного изохинолонас каталитическим доменом C // Фармация и фармакология. 2014. №1 (2). С. 3–7. doi: 10.19163/2307-9266-2014-2-1(2)-3-7
  10. Норман Г.Э., Стегайлов В.В. Стохастическая теория метода классической молекулярной динамики // Матем. Моделирование. 2012. № 6. C. 3–44.
  11. Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G., Corvol P. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning // Proc. Natl. Acad. Sci. U. S. A. 1988. N. 85. P. 9386–9390.
  12. Corradi H.R., Schwager S.L.U., Nchinda A.T., Sturrock E.D., Acharya K.R. Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design // J. Mol. Biol. 2006. N. 357. P. 964–974. DOI: http: 10.1016/j.jmb.2006.01.048
  13. Natesh R., Schwager S. L. U., Sturrock E. D., Acharya K. R. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex // Nature. 2003. N. 421. P. 551–554. DOI: http://dx.doi.org/ 10.1038/nature01370
  14. Akif M., Georgiadis D., Mahajan A., Dive V., Sturrock E.D., Isaac R.E., Acharya K.R. High resolution crystal structures of drosophila melanogaster angiotensin converting enzyme in complex with novel inhibitors and antihypertensive drugs // J. Mol. Biol. 2010. N 400. P. 502–517. doi: 10.1016/j.jmb.2010.05.024
  15. Teppen B.J. HyperChem, release 2: molecular modeling for the personal computer // J. Chem. Inf. Comput. Sci. 1992. V. 32. P. 757–759.
  16. Stephens P.J., Devlin F.J., Chabalowski C.F., Frisch M.J. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields // J. Phys. 1994. N. 98 (45). P. 11623–11627. doi: 10.1021/j100096a001
  17. Минкин В.И., Симкин Б.Я., Миняев Р.М. Строение молекул. Ростов-на-Дону: Феникс, 1997. 560 с.
  18. Гендугов Т.А., Щербакова Л.И., Глушко А.А., Кодониди И.П., Сочнев В.С. Изучение взаимодействия производных 4-оксопиримидина с активным центром циклооксигеназы-2 методом молекулярной динамики // Современные проблемы науки и образования. 2015. №2. URL: https://science-education.ru/ru/article/view?id=22796 (дата обращения: 10.06.2017).
  19. Халилова С.В. Моделирование процесса жидкостной экстракции биологически активных веществ методом молекулярной динамики в программе Биоэврика // Сборник материалов VI Всероссийской научной конференции студентов и аспирантов с международным участием «Молодая фармация – потенциал будущего». Санкт-Петербург, 25–26 апреля 2016 г. СПб.: Изд-во СПХФА. 2016. C. 118–120.
  20. Cornell W.D., Cieplak P., Bayly C.I., Gould I.R., Merz K.M., Ferguson D.M., Spellmeyer D.C., Fox T., Caldwell J.W., Kollman P.A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules // J. Am. Chem. Soc. 1995. N. 117 (19). P. 5179–5197. doi: 10.1021/ja00124a002
  21. Leontyev I.V., Stuchebrukhov A.A. Polarizable mean-field model of water for biological simulations with AMBER and CHARMM force fields // J. Chem. Theory Comput. 2012. N. 8 (9). P. 3207–3216. doi: 10.1021/ct300011h
  22. Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., Klein M.L. Comparison of simple potential functions for simulating liquid water // J. Chem. Phys. 1983. V. 79. N. 2. P. 926–935. doi: 10.1063/1.445869
  23. Berendsen H.J.C., Postma J.P.M., van Gunsteren W.F., DiNola A., Haak J.R.. Molecular dynamics with coupling to an external bath // J. Chem. Phys. 1984. N. 81. P. 3684–3690. doi: 10.1063/1.448118
  24. Forli S., Huey R., Pique M.E., Sanner M.F., Goodsell D.S., Olson A.J. Computational protein–ligand docking and virtual drug screening with the AutoDock suite // Nature Protocols. 2016. V. 11. N. 5. P. 905–919. doi: 10.1038/nprot.2016.051
  25. Hildebrandt A.K., Dietzen M., Lengauer T., Lenhof H.P., Althaus E., Hildebrandt A.
  26. Efficient computation of root mean square deviations under rigid transformations // J. Comput. Chem. 2014. N. 35 (10). P. 765-771. doi: 10.1002/jcc.23513

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Glushko A.A., Chiriapkin A.S., Chiriapkin V.S., Murtuzalieva A.M., Polkovnikova Y.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 67428 от 13.10.2016.