Skip to main content
SpringerLink
Log in

Predicting conformations and orientations of guests within a water soluble host: a molecular docking approach

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

In this study we have examined conformations and orientations of guests within a water-soluble host known by the trivial name Octa Acid (OA). Docking program Vina, which was originally developed for screening drug-like molecules, has been used to identify binding modes and affinities of select guest molecules with OA. Hydrophobic guests were encapsulated into the nonpolar cavity of OA capsule owing to solvophobic interactions. Amphiphilic guests were bound by keeping the nonpolar part within the cavity of OA, while pointing the polar anionic group out of the cavity. All these results obtained from the docking study were in accord with experimental findings. The post-complexation attributes of the guests were regulated by available free space and the specific interactions between guest–OA pair, which led to unusual conformations and orientations. This study showed that scoring function available with Vina, which was derived from protein–ligand data set, could successfully predict post-complexed structural features of guests within OA, thus opening opportunities to modulate physical and chemical behavior of guest molecules.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zarra, S., Wood, D.M., Roberts, D.A., Nitschke, J.R.: Molecular containers in complex chemical systems. Chem. Soc. Rev. 44, 419–432 (2015)

    Article  CAS  Google Scholar 

  2. Lehn, J.-M.: Toward self-organization and complex matter. Science. 295, 2400–2403 (2002)

    Article  CAS  Google Scholar 

  3. Oshovsky, G.V., Reinhoudt, D.N., Verboom, W.: Supramolecular chemistry in water. Angew. Chem. Int. Ed. 46, 2366–2393 (2007)

    Article  CAS  Google Scholar 

  4. Schrader, T., Hamilton, A.D.: Functional synthetic receptors. Wiley-VCH, Weinheim (2005)

    Book  Google Scholar 

  5. Ariga, K., Kunitake, T.: Supramolecular chemistry–fundamentals and applications. Springer, Berlin (2005)

    Google Scholar 

  6. Laughrey, Z., Gibb, B.C.: Water-soluble, self-assembling container molecules: An update. Chem. Soc. Rev. 40, 363–386 (2011)

    Article  CAS  Google Scholar 

  7. Hof, F., Rebek, J. Jr.: Molecules within molecules: Recognition through self-assembly. PNAS. 99, 4775–4777 (2002)

    Article  CAS  Google Scholar 

  8. Southall, N.T., Ken, A.D., Haymet, A.D.J.: A view of the hydrophobic effect. J. Phys. Chem. B. 106, 521–533 (2002)

    Article  CAS  Google Scholar 

  9. Rekharsky, M.V., Mayhew, M.P., Goldberg, R. N., Ross, P.D., Yamashoji, Y., Inoue, Y.: Thermodynamic and nuclear magnetic resonance study of the reactions of α-and β-cyclodextrin with acids, aliphatic amines, and cyclic alcohols. J. Phys. Chem. B. 101, 87–100 (1997)

    Article  CAS  Google Scholar 

  10. Guo, D.S., Uzunova, V.D., Assaf, K.I., Lazar, A.I., Liu, Y., Nau, W.M.: Inclusion of neutral guests by water-soluble macrocyclic hosts—a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils. Supramol. Chem. 28, 384–395 (2016).

    Article  CAS  Google Scholar 

  11. Williams, D.H., Stephens, E., O’Brien, D.P., Zhou, M.: Understanding noncovalent interactions: Ligand binding energy and catalytic efficiency from ligand-induced reductions in motion within receptors and enzymes. Angew. Chem. Int. Ed. 43, 6596–6616 (2004)

    Article  CAS  Google Scholar 

  12. Gung, B.W., Xue, X., Zou, Y.: Enthalpy (∆H) and entropy (∆S) for π-stacking interactions in near-sandwich configurations: The relative importance of electrostatic, dispersive, and charge-transfer effects. J. Org. Chem. 72, 2469–2475 (2007)

    Article  CAS  Google Scholar 

  13. Gibb, C.L.D., Gibb, B.C.: Templated assembly of water-soluble nano-capsules: Inter-phase sequestration, storage, and separation of hydrocarbon gases. J. Am. Chem. Soc. 128, 16498–16499 (2006)

    Article  CAS  Google Scholar 

  14. Jayaraj, N., Zhao, Y., Parthasarathy, A., Porel, M., Liu, R.S.H., Ramamurthy, V.: Nature of supramolecular complexes controlled by the structure of the guest molecules: Formation of Octa Acid based capsuleplex and cavitandplex. Langmuir. 25, 10575–10586 (2009)

    Article  CAS  Google Scholar 

  15. Choudhury, R., Barman, A., Prabhakar, R., Ramamurthy, V.: Hydrocarbons depending on the chain length and head group adopt different conformations within a water-soluble nanocapsule: 1H NMR and molecular dynamics studies. J. Phys. Chem. B. 117, 398–407 (2013)

    Article  CAS  Google Scholar 

  16. Ramamurthy, V., Sivaguru, J.: Supramolecular photochemistry as a potential synthetic tool: Photocycloaddition. Chem. Rev. 116, 9914–9993 (2016)

    Article  CAS  Google Scholar 

  17. Ramamurthy, V.: Photochemistry within a water-soluble organic capsule. Acc. Chem. Res. 48, 2904–2917 (2015)

    Article  CAS  Google Scholar 

  18. Gupta, S., Choudhury, R., Krois, D., Brinker, U.H., Ramamurthy, V.: Cucurbituril adamantanediazirine complexes and consequential carbene chemistry. J. Org. Chem. 77, 5155–5160 (2012)

    Article  CAS  Google Scholar 

  19. Parthasarathy, A.; Ramamurthy, V. Water-soluble Octa Acid capsule as a reaction container: Templated photodimerization of indene in water. J. Photochem. Photobiol. A, 317, 132–139 (2016).

    Article  CAS  Google Scholar 

  20. Trott, O., Olson, A.J.: AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455–461 (2009)

    Google Scholar 

  21. Halgren, T. A.: Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 17, 490–519 (1996)

    Article  CAS  Google Scholar 

  22. Spoel, V.D., Lindahl, E., Hess, B., Groenhof, G., Mark, A.E., Berendsen, H.J.: GROMACS: fast, flexible, and free. Comput. Chem. 26, 1701–1718 (2005)

    Article  Google Scholar 

  23. Kaminski, A.G., Friesner, A.R., Tirado-Rives, J., Jorgensen, L.W.: Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B. 105, 6474–6487 (2001)

    Article  CAS  Google Scholar 

  24. Jorgensen, L.W., Tirado-Rives, J.: The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc. 110, 1657–1666 (1988)

    Article  CAS  Google Scholar 

  25. Ribeiro, A.A.S.T., Horta, B.A.C., de Alencastro, R.B.: MKTOP: a program for automatic construction of molecular topologies. J. Braz. Chem. Soc. 19, 1433–1435 (2008)

    Article  CAS  Google Scholar 

  26. Breneman, C. M., Wiberg, K. B.: Determining atom-centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis. J. Comput. Chem. 11, 361–373 (1990)

    Article  CAS  Google Scholar 

  27. Lee, C., Yang, W., Parr, R.G.: Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B. 37, 785 (1988)

    Article  CAS  Google Scholar 

  28. Becke, A.D.: Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A. 38, 3098 (1988)

    Article  CAS  Google Scholar 

  29. Frish, M.J. et al.: Gaussian 98, revision A.9; Pittsburgh, PA, 1998

  30. Darden, T., York, D., Pederson, L.: Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089 (1993)

    Article  CAS  Google Scholar 

  31. Humphrey, W., Dalke, A., Schulten, K.: VMD: Visual molecular dynamics. J. Mol. Graphics. 14, 33–38 (1996)

    Article  CAS  Google Scholar 

  32. DeLano, W.L.: The PyMOL molecular graphics system. DeLano Scientific, San Carlos (2002)

  33. Turro, N.J., Ramamurthy, V., Scaiano, J.C.: Modern molecular photochemistry of organic molecules. University Science Books, Sausalito (2010)

    Google Scholar 

  34. Gibb, C.L.D., Sundaresan, A.K., Ramamurthy, V., Gibb, B.C.: J. Am. Chem. Soc. 130, 4069–4080 (2008)

    Article  CAS  Google Scholar 

  35. Sundaresan, A.K., Ramamurthy, V.: Consequences of controlling free space within a reaction cavity with a remote alkyl group: photochemistry of para-alkyl dibenzyl ketones within an organic capsule in water. Photochem. Photobiol. Sci. 7, 1555–1564 (2008)

    Article  CAS  Google Scholar 

  36. Samanta, S.R., Choudhury, R., Ramamurthy, V.: Photoisomerization and photooxygenation of 1, 4-diaryl-1,3-dienes in a confined Space. J. Phys. Chem. A. 118, 10554–10562 (2014)

    Article  CAS  Google Scholar 

  37. Gupta, S., Choudhury, R., Krois, D., Wagner, G., Brinker, U.H., Ramamurthy, V.: Photochemical generation and reactivity of carbenes within an organic cavitand and capsule: Photochemistry of adamantanediazirines. Org. Lett. 13, 6074–6077 (2011)

    Article  CAS  Google Scholar 

  38. Choudhury, R., Gupta, S., Da Silva, J.P., Ramamurthy, V: Deep-cavity cavitand Octa Acid as a hydrogen donor: Photofunctionalization with nitrenes generated from azidoadamantanes. J. Org. Chem. 78, 1824–1832 (2013)

    Article  CAS  Google Scholar 

  39. Kitchen, D.B., Decornez, H., Furr, J.R., Bajorath, J.: Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. 3, 935–949 (2004)

    CAS  Google Scholar 

  40. Jaghoori, M.M., Bleijlevens, B., Olabarriaga, S.D.: 1001 ways to run AutoDock Vina for virtual screening. J. Comput. Aided Mol. Des. 30, 237–249 (2016)

    Article  CAS  Google Scholar 

  41. Gibb, C.L.D., Gibb, B.C.: Binding of cyclic carboxylates to octa-acid deep-cavity cavitand. J. Comput. Aided Mol. Des. 28, 319–325 (2014)

    Article  CAS  Google Scholar 

  42. Gallicchio, E., Chen, H., Chen, H., Fitzgerald, M., Gao, Y., He, P., Kalyanikar, M., Chuan, K., Lu, B., Niu, Y., Pethe, M., Zhu, J., Levy, R.M.: BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge. J. Comput. Aided Mol. Des. 29, 315–325 (2015)

    Article  CAS  Google Scholar 

  43. Jayaraj, N., Jagadesan, P., Samanta, S.R., Da Silva, J.P., Ramamurthy, V.: Release of guests from encapsulated masked hydrophobic precursors by a photo-trigger. Org. Lett. 15, 4374–4377 (2013)

    Article  CAS  Google Scholar 

  44. Jagadesan, P., Da Silva, J.P., Givens, R.S., Ramamurthy, V.: Photorelease of incarcerated guests in aqueous solution with phenacylesters as the trigger. Org. Lett. 17, 1276–1279 (2015)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physical Sciences, Arkansas Tech University, Russellville, AR, 72801, USA

    Kassandra Cendejas & Rajib Choudhury

Authors
  1. Kassandra Cendejas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajib Choudhury
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajib Choudhury.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 4617 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cendejas, K., Choudhury, R. Predicting conformations and orientations of guests within a water soluble host: a molecular docking approach. J Incl Phenom Macrocycl Chem 87, 349–356 (2017). https://doi.org/10.1007/s10847-017-0707-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-017-0707-7

Keywords

Search

Navigation