Journal of Molecular Modeling

, 17:2169 | Cite as

Do the substituent effects affect conformational freedom of squalene in hopene biosynthesis?

Original Paper

Abstract

The analysis of biochemical processes is one of the main challenges for modern computational chemistry. Probably the biggest issue facing scientists in this case is the number of factors that have to be taken into account, as even those factors that do not seem to be meaningful may eventually be crucial. Such a belief led to the investigation on the substituent effects during squalene cyclization process. We focused on the formation of lanosterol ring A through squalene epoxide and an analogue process observed in bacteria, leading to the hopene formation without an intermediate oxide. Interestingly, our results indicate that, opposite of chemical intuition, a more substituted chain is more likely to adopt a conformation suitable for the cyclization process. Presumably the rational for this behavior is the presence of intermolecular CH⋅⋅⋅π interactions between the hydrogen atoms from methyl groups and the squalene π bonds in the open-chain structure. The effect seems to have a firm impact on the hopene formation process. Calculations were performed using two different methods: MP2 and M06-2X, combined with the cc-pVDZ basis set.

Keywords

Conformational freedom Hopene Lanosterol Squalene Substituent effects 

Supplementary material

894_2011_1103_MOESM1_ESM.pdf (399 kb)
Esm 1(PDF 399 kb)

References

  1. 1.
    Hoffmann RW (2000) Conformation design of open-chain compounds. Angew Chem Int Ed Eng 39:2054–2070CrossRefGoogle Scholar
  2. 2.
    Alder RW, Allen PR, Anderson KR, Butts CP, Khosravi E, Martín A, Maunder CM, Orpen AG, St Pourcain ChB (1998) Conformational control by quaternary centres: theory, database evidence and application to polymers. J Chem Soc Perkin Trans 2:2083–2107Google Scholar
  3. 3.
    Hoffmann RW, Schopfer U, Stahl M (1997) Z- and U-shaped open chain molecular backbones by conformation design. Tetrahedron Lett 38:4055–4058CrossRefGoogle Scholar
  4. 4.
    Wendt KU, Schulz GE, Corey EJ, Liu DR (2833) (2000) Enzyme mechanisms for polycyclic triterpene formation. Angew Chem Int Edn 39:2812Google Scholar
  5. 5.
    Frisch MJ et al. (2004) Gaussian 03. Gaussian Inc, Wallingford, CTGoogle Scholar
  6. 6.
    Møller C, Plesset MS (1934) Note on an approximation treatment for many-electron systems. Phys Rev 46:618–622CrossRefGoogle Scholar
  7. 7.
    Zhao Y, Truhlar DG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41:157–167CrossRefGoogle Scholar
  8. 8.
    Jensen F (2002) Polarization consistent basis sets III. The importance of diffuse functions. J Chem Phys 117:9234–9240CrossRefGoogle Scholar
  9. 9.
    Thoma R, Schulz-Gasch T, D’Arcy B, Benz J, Aebi J, Dehmlow H, Hennig M, Stihle M, Ruf A (2004) Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature 432:118–122CrossRefGoogle Scholar
  10. 10.
    Hoshino T, Sato T (2002) Squalene—Hopene cyclase: catalytic mechanism and substrate recognition. Chem Commun (Camb) 4:291–301CrossRefGoogle Scholar
  11. 11.
    Leong MK, Mastryukov VS, Boggs JE (1994) Structure and conformations of six-membered systems A6H12 (A = C, Si): ab initio study of cyclohexane and cyclohexasilane. J Phys Chem 98:6961–6966CrossRefGoogle Scholar
  12. 12.
    Allinger NL, Miller MA (1961) Conformational analysis. XVII.1 The 1,3-diaxial methyl-methyl interaction. J Am Chem Soc 83:2145–2146CrossRefGoogle Scholar
  13. 13.
    Nishio M, Hirota M, Umezaw Y (1998) The CH-[pi] interaction: evidence, nature, and consequences. Wiley, New YorkGoogle Scholar
  14. 14.
    Umezawaa Y, Tsuboyamab S, Takahashib H, Uzawab J, Nishio M (1999) CH/π interaction in the conformation of organic compounds. A database study. Tetrahedron 55:10047–10056CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.BioInfoBank InstitutePoznańPoland
  2. 2.Institute for Medical BiologyPolish Academy of SciencesLodzPoland
  3. 3.Quantum Chemistry Group, Department of ChemistryAdam Mickiewicz UniversityPoznanPoland

Personalised recommendations