The SOL docking package for computer-aided drug design

Authors

Keywords:

computer-aided drug design, docking, genetic algorithms, global optimization, MMFF94 force field, solvatation model, virtual screening

Abstract

A new program package for docking of a flexible ligands into the active sites of proteins as well as into other biological targets is discussed. The initial validation is also described. It is known that the docking procedure is a main tool in modern computer-aided drug design processes. In our program we use the genetic algorithm to optimize the ligand’s inner torsion degrees of freedom and a rotational-translational position of ligand as a whole in a target active site. The optimization is guided by estimating the inner ligand energy and the energy of ligand’s interaction with biological micromolecules. The calculations of these energies are performed in the framework of the MMFF94 force field model. Solvation-desolvation effects are considered via Generalized Born Approximation. The program also calculates the estimate of ligand-target binding free energy and performs the clusterization of solutions (ligand’s poses) according to its geometries. The data from the initial validation show that our program can perform the successful positioning of ligands in protein’s active sites as well as virtual screening for active ligands in database which contains active and inactive compounds. Keywords: computer-aided drug design, docking, genetic algorithms, global optimization, MMFF94 force field, solvatation model, virtual screening

Author Biographies

A.N. Romanov

Lomonosov Moscow State University,
Research Computing Center

F.V. Grigoriev

Lomonosov Moscow State University,
Research Computing Center

S.V. Luschekina

Lomonosov Moscow State University,
Research Computing Center

Ya.B. Martynov

Lomonosov Moscow State University,
Research Computing Center

V.B. Sulimov

Lomonosov Moscow State University,
Research Computing Center

O.A. Kondakova

Dimonta, LLC

A.V. Sulimov

Dimonta, LLC

References

  1. Gani O.A. B.S.M. Signposts of docking and scoring in drug design // Chem. Biol. Drug Des. 2007. 70. 360-365.
  2. Klebe G. Virtual ligand screening: strategies, perspectives and limitations // Drug Discovery Today. 2006. 11. 580-594.
  3. Kitchen D.B., Decornez H., Furr J.R., Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications // Nat. Rev. Drug Discov. 2004. 3. 935-949.
  4. Lyne P.D. Structure-based virtual screening: an overview // Drug Discovery Today. 2002. 7. 1047-1055.
  5. Sousa S.F., Fernandes P.A., Ramos M.J. Protein-ligand docking: current status and future challenges // Proteins: Struct., Funct. and Bioinf. 2006. 65. 15-26. Virtual screening in drug discovery // Alvarez J., Shoichet B. (Eds.). Boca Raton: Taylor &; Francis, 2005.
  6. Goodsell D.S., Olson A.J. Automated docking of substrates to proteins by simulated annealing // Proteins: Structure, Function and Genetics. 1990. 8. 195-202.
  7. Goodsell D.S., Morris G.M., Olson A.J. Automated docking of flexible ligands: applications of AutoDock // J. Mol. Recognition. 1996. 9. 1-5.
  8. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., Olson A.J. Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function // J. Comp. Chem. 1998. 19. 1639-1662.
  9. Holland J.H. Adaptation in natural and artificial systems. Ann Arbor: University of Michigan Press, 1975.
  10. Goldberg D.E. Genetic algorithms in search, optimization, and machine learning. Reading: Addison-Wesley, 1989.
  11. Goldberg D.E. Real-coded genetic algorithm, virtual alphabets, and blocking // Complex Systems. 1991. 5. 139-167.
  12. Goldberg D.E., Deb K. A comparative analysis of selection schemes used in genetic algorithms // Foundations of Genetic Algorithms. Rawlins G.J. E. (Ed.). San Mateo: Morgan Kaufmann, 1991. 69-93.
  13. Oshiro C.M., Kuntz I.D., Dixon J.S. Flexible ligand docking using a genetic algorithm // J. Comput.-Aided Mol. Design. 1995. 9. 113-130.
  14. Westhead D.R., Clark D.E., Frenkel D., Li J., Murray C.W., Robson B., Waszkowycz B. PRO-LIGAND: An approach to de novo molecular design. 3. A genetic algorithm for structure refinement // J. Comput.-Aided Mol. Design. 1995. 9. 139-148.
  15. Clark D.E., Westhead D.R. Evolutionary algorithms in computer-aided molecular design // J. Comput.-Aided Mol. Design. 1996. 10. 337-358.
  16. Pegg S.C.-H., Haresco J.J., Kuntz I.D. A genetic algorithm for structure-based de novo design // J. Comput.-Aided Mol. Design. 2001. 15. 911-933.
  17. Sulimov V., Romanov A., Grigoriev F., Kondakova O., Sulimov A., Bryzgalov P., Zhabin S., Chernobrovkin A., Sobolev S. Web-oriented system Keenbase for virtual screening and design of new ligands for biological macromolecules. Application for new drug searches // Proc. of the St. Petersburg Int. Workshop on NanoBiotechnologies, 27-29, November, 2006. St. Petersburg, 2006. 33-34.
  18. Sulimov A.V., Sulimov V.B., Romanov A.N., Grigoriev F.V., Kondakova O.A., Bryzgalov P.A., Ostapenko D.A. Web-oriented system Keenbase for new drugs design // Proc. of the Fourth Int. Symposium on Computational Methods in Toxicology and Pharmacology Integrating Internet Resourses (CMPTI-2007, Moscow, Russia, September, 1-5, 2007). Moscow, 2007. 158.
  19. Сулимов В.Б., Романов А.Н., Григорьев Ф.В., Кондакова О.А., Сулимов А.В., Жабин С.Н., Соболев С.И. Веб-ориентированная система молекулярного моделирования Keenbase для разработки новых лекарств // Тр. Всероссийской научной конференции «Научный сервис в сети Интернет: технологии параллельного программирования», 18-23 сентября, 2006, Новороссийск. М.: Изд-во Моск. ун-та, 170-172.
  20. Воеводин Вл.В., Филамофитский М.П. X-Com - проект организации распределенных вычислений // Тр. Всероссийской научной конференции «Научный сервис в сети Интернет». М.: Изд-во Моск. ун-та, 2001. 11-13.
  21. Филамофитский М.П. Система поддержки метакомпьютерных расчетов X-Com: архитектура и технология работы // Вычислительные методы и программирование. 2004. 5, № 1. 128-136. http://www.parallel.ru
  22. Halgren T.A. Merck molecular force field. I. Basis, form, scope, parametrization and performance of MMFF94 // J. of Comp. Chem. 1996. 5 &; 6. 490-519.
  23. Halgren T.A. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions // J. of Comp. Chem. 1996. 5 &; 6. 520-552.
  24. Halgren T.A. Merck molecular force field. III. Molecular geometries and vibrational frequencies for MMFF94 // J. of Comp. Chem. 1996. 5 &; 6. 553-586.
  25. Halgren T.A., Nachbar R.B. Merck molecular force field. IV. Conformational energies and geometries for MMFF94 // J. of Comp. Chem. 1996. 5 &; 6. 587-615.
  26. Halgren T.A. Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data and empirical rules // J. of Comp. Chem. 1996. 5 &; 6. 616-641.
  27. Goodford P.J. A computational procedure for determining energetically favorable binding sites on biologically important macromolecules // J. Med. Chem. 1985. 28. 849-857.
  28. Romanov A.N., Jabin S.N., Martynov Y.B., Sulimov A.V., Grigoriev F.V., Sulimov V.B. Surface generalized Born method: a simple, fast and precise implicit solvent model beyond the Coulomb approximation // J. Phys. Chem. A. 2004. 108. 9323-9327.
  29. Bordner A.J., Cavasotto C.N., Abagyan R.A. Accurate transferable model for water, n-octanol, and n-hexadecane solvation free energies // J. Phys. Chem. B. 2002. 106. 11009-11015.
  30. Ghosh A., Rapp C.S., Friesner R.A. Generalized Born model based on a surface integral formulation // J. Phys. Chem. B. 1998. 102. 10983-10990.
  31. Григорьев Ф.В., Романов А.Н., Кондакова О.А., Лущекина С.В., Сулимов В.Б. Алгоритм расстановки силовых параметров на атомах органических молекул и белков в рамках силового поля MMFF 94 // Вычислительные методы и программирование. 2006. 7. 128-136.
  32. Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissing H., Shindyalov I.N., Bourne P.E. The protein data bank // Nucleic Acids Res. 2000. 28. 235-242.
  33. Word J.M., Lovell S.C., Richardson J.S., Richardson D.C. Asparagine and glutamine: using hydrogen atom contacts in the choice of sidechain amide orientation // J. Mol. Biol. 1999. 285. 1733-1745. NCI (National cancer institute) diversity data base // (http://dtp.nci.nih.gov/docs/3d_database/Structural_information/structural_data.html).
  34. Stahl M., Rarey M. Detailed analysis of scoring functions for virtual screening // J. Med. Chem. 2001. 44. 1035-1042.
  35. Gasteiger J., Rudolph C., Sadowski J. Automatic generation of 3D-atomic coordinates for organic molecules // Tetrahedron Comput. Methodol. 1990. 3. 537-547.
  36. Maruyama I. // Jpn. J. Clin. Hematol. 1990. 31. 776-781.
  37. Kikumoto R., Tamao Y., Tezuka T., Tonomura A., Hara H., Ninomiya K.,
  38. Hijikata A., Okamoto S. Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]-L-arginyl]-2-piperidinecarboxylic acid // Biochemistry. 1984. 23. 85-90.
  39. Okamoto S., Hijikata A. Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion // Biochemical and Biophysical Research Communications. 1981. 101. 440-446.
  40. Linder R., Frebelius S., Jansson K., Swedwnborg J. Inhibition of endothelial cell-mediated generation of activated protein C by direct and antithrombin-dependent thrombin inhibitors // Blood Coagulation and Fibrinolysis. 2003. 14. 139-146.
  41. Okamoto S., Hijikata-Okunomiya A. Synthetic selective inhibitors of thrombin // Methods in Enzymology. 1993. 222. 328-340.
  42. Hijikata-Okunomiya A., Okamoto S. A strategy for a rational approach to designing synthetic selective inhibitors // Seminars in Thrombosis and Hemostasis. 1992. 18. 135-140.
  43. Vacca J. New advances in the discovery of thrombin and factor Xa inhibitors // Current Opinion in Chemical Biology. 2000. 4. 394-400.
  44. Steinmetzer T., Hauptmann J., Sturzebecher J. Advances in the development of thrombin inhibitors // Exp. Opin. Invest. Drugs. 2001. 10. 845-864.
  45. Shafer J.A. Cardiovascular chemotherapy: anticoagulants // Current Opinion in Chemical Biology. 1998. 2. 458-465.
  46. Hauptmann J., Sturzebecher J. Synthetic inhibitors of thrombin and factor Xa: from bench to bedside // Thrombosis Research. 1999. 93. 203-241.
  47. Varma S. // 3d US Catalyst User’s Group meeting Boehringer-Ingelheim pharmaceuticals, Inc. May 11, 2001.
  48. Pauls H.W., Ewing W.R., Choi-Sledeski Y.M. The design of competitive, small-molecule inhibitors of coagulation factor Xa // Frontiers Med. Chem. 2004. 1. 129-152. http://www.ccdc.cam.ac.uk/products/life_sciences/validate
  49. Frenkel E.P., Shen Y.M., Haley B.B. The direct thrombin inhibitors: their role and use for rational anticoagulation // Hematol. Oncol. Clin. N. Am. 2005. 19. 119-145.
  50. Синауридзе Е.И., Сулимов В.Б., Семенов В.В., Грибкова И.В., Горбатенко А.С.,
  51. Боголюбов А.А., Романов А.Н., Кондакова О.А., Атауллаханов Ф.И. Новый ряд ингибиторов тромбина // Тр. IV Международного конгресса «Биотехнология: состояние и перспективы развития», 12-16 марта 2007, Москва. Часть 1. М.: 2007, 103.
  52. Романов А.Н., Сулимов В.Б., Кондакова О.А., Синауаридзе Е.И., Кузнецов Ю.В., Воеводин В.В., Атауллаханов Ф.И. Новые ингибиторы тромбина: молекулярный дизайн с использованием суперкомпьютеров и экспериментальное подтверждение активности // Тр. IV Сибирской школы-семинара по параллельным и высокопроизводительным вычислениям. Томск, 2007. 18-19.
  53. Грибкова И.В., Синауридзе Е.И., Сулимов В.Б., Горбатенко А.С., Кузнецов Ю.В., Монаков М.Ю., Боголюбов А.А., Романов А.Н., Кондакова О.А., Атауллаханов Ф.И. Поиск новых ингибиторов тромбина // Тр. XI Международной Пущинской школы-конференции молодых ученых 29 октября -2 ноября 2007. Пущино, 2007. 240-241.
  54. Sulimov V.B., Romanov A.N., Kondakova O.A., Sinauridze E.I., Butylin A.A., Gribkova I.V.,
  55. Gorbatenko A.S., Bogoliubov A.A., Titov I.Yu., Polunin E.V., Kuznetsov Yu.V., Taidakov I.V.,
  56. Voevodin V.V., Sobolev S.I., Ataullakhanov F.I. New thrombin inhibitors: molecular design and experimental discovery // (IDDST), BIT’s 5th Anniversary Congress of International Drug Discovery Science &; Technology, Serial II: Advances and Challenges Toward Major Diseases. Theme: Extension on New Hope, November 7-13, 2007. Xián &; Beijing, China.
  57. Синауридзе Е.И., Горбатенко А.С., Грибкова И.В., Сулимов В.Б., Романов А.Н., Кондакова О.А., Ажигирова М.А., Дереза Т.Л., Кузнецов Ю.В., Боголюбов А.А., Атауллаханов Ф.И. Гиперкоагуляция, вызываемая разбавлением плазмы искусственными плазмозамещающими растворами // Технологии живых систем. 2008. 5, № 1. 3-14.
New computational technologies

Downloads

Published

03-07-2008

How to Cite

Романов А., Григорьев Ф., Лущекина С., Мартынов Я., Сулимов В., Кондакова О., Сулимов A. The SOL Docking Package for Computer-Aided Drug Design // Numerical Methods and Programming (Vychislitel’nye Metody i Programmirovanie). 2008. 9. 213-233

Issue

Vol. 9 (2008): Issue 3.

Section

Section 1. Numerical methods and applications

Most read articles by the same author(s)

1 2 3 > >>