Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 2002 Apr;82(4):1791–1808. doi: 10.1016/s0006-3495(02)75530-6

Long time dynamics of Met-enkephalin: comparison of explicit and implicit solvent models.

Min-yi Shen My 1, Karl F Freed 1
PMCID: PMC1301977  PMID: 11916839

Abstract

Met-enkephalin is one of the smallest opiate peptides. Yet, its dynamical structure and receptor docking mechanism are still not well understood. The conformational dynamics of this neuron peptide in liquid water are studied here by using all-atom molecular dynamics (MD) and implicit water Langevin dynamics (LD) simulations with AMBER potential functions and the three-site transferable intermolecular potential (TIP3P) model for water. To achieve the same simulation length in physical time, the full MD simulations require 200 times as much CPU time as the implicit water LD simulations. The solvent hydrophobicity and dielectric behavior are treated in the implicit solvent LD simulations by using a macroscopic solvation potential, a single dielectric constant, and atomic friction coefficients computed using the accessible surface area method with the TIP3P model water viscosity as determined here from MD simulations for pure TIP3P water. Both the local and the global dynamics obtained from the implicit solvent LD simulations agree very well with those from the explicit solvent MD simulations. The simulations provide insights into the conformational restrictions that are associated with the bioactivity of the opiate peptide dermorphin for the delta-receptor.

Full Text

The Full Text of this article is available as a PDF (847.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barrow C. J., Zagorski M. G. Solution structures of beta peptide and its constituent fragments: relation to amyloid deposition. Science. 1991 Jul 12;253(5016):179–182. doi: 10.1126/science.1853202. [DOI] [PubMed] [Google Scholar]
  2. Deber C. M., Behnam B. A. Role of membrane lipids in peptide hormone function: binding of enkephalins to micelles. Proc Natl Acad Sci U S A. 1984 Jan;81(1):61–65. doi: 10.1073/pnas.81.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Duan Y., Kollman P. A. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. Science. 1998 Oct 23;282(5389):740–744. doi: 10.1126/science.282.5389.740. [DOI] [PubMed] [Google Scholar]
  4. Eisenberg D., McLachlan A. D. Solvation energy in protein folding and binding. Nature. 1986 Jan 16;319(6050):199–203. doi: 10.1038/319199a0. [DOI] [PubMed] [Google Scholar]
  5. Fändrich M., Fletcher M. A., Dobson C. M. Amyloid fibrils from muscle myoglobin. Nature. 2001 Mar 8;410(6825):165–166. doi: 10.1038/35065514. [DOI] [PubMed] [Google Scholar]
  6. Garemyr R., Elofsson A. Study of the electrostatics treatment in molecular dynamics simulations. Proteins. 1999 Nov 15;37(3):417–428. doi: 10.1002/(sici)1097-0134(19991115)37:3<417::aid-prot9>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  7. Graham W. H., Carter E. S., 2nd, Hicks R. P. Conformational analysis of Met-enkephalin in both aqueous solution and in the presence of sodium dodecyl sulfate micelles using multidimensional NMR and molecular modeling. Biopolymers. 1992 Dec;32(12):1755–1764. doi: 10.1002/bip.360321216. [DOI] [PubMed] [Google Scholar]
  8. Hughes J., Smith T. W., Kosterlitz H. W., Fothergill L. A., Morgan B. A., Morris H. R. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature. 1975 Dec 18;258(5536):577–580. doi: 10.1038/258577a0. [DOI] [PubMed] [Google Scholar]
  9. Isogai Y., Némethy G., Scheraga H. A. Enkephalin: conformational analysis by means of empirical energy calculations. Proc Natl Acad Sci U S A. 1977 Feb;74(2):414–418. doi: 10.1073/pnas.74.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kirshenbaum K., Daggett V. pH-dependent conformations of the amyloid beta(1-28) peptide fragment explored using molecular dynamics. Biochemistry. 1995 Jun 13;34(23):7629–7639. doi: 10.1021/bi00023a009. [DOI] [PubMed] [Google Scholar]
  11. Kostov K. S., Freed K. F. Long-time dynamics of Met-enkephalin: comparison of theory with Brownian dynamics simulations. Biophys J. 1999 Jan;76(1 Pt 1):149–163. doi: 10.1016/S0006-3495(99)77185-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Li Z., Scheraga H. A. Monte Carlo-minimization approach to the multiple-minima problem in protein folding. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6611–6615. doi: 10.1073/pnas.84.19.6611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ooi T., Oobatake M., Némethy G., Scheraga H. A. Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. Proc Natl Acad Sci U S A. 1987 May;84(10):3086–3090. doi: 10.1073/pnas.84.10.3086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Paine G. H., Scheraga H. A. Prediction of the native conformation of a polypeptide by a statistical-mechanical procedure. I. Backbone structure of enkephalin. Biopolymers. 1985 Aug;24(8):1391–1436. doi: 10.1002/bip.360240802. [DOI] [PubMed] [Google Scholar]
  15. Pasternak G. W. Multiple morphine and enkephalin receptors and the relief of pain. JAMA. 1988 Mar 4;259(9):1362–1367. [PubMed] [Google Scholar]
  16. Richards F. M. Areas, volumes, packing and protein structure. Annu Rev Biophys Bioeng. 1977;6:151–176. doi: 10.1146/annurev.bb.06.060177.001055. [DOI] [PubMed] [Google Scholar]
  17. Roques B. P., Garbay-Jaureguiberry C., Oberlin R., Anteunis M., Lala A. K. Conformation of Met5-enkephalin determined by high field PMR spectroscopy. Nature. 1976 Aug 26;262(5571):778–779. doi: 10.1038/262778a0. [DOI] [PubMed] [Google Scholar]
  18. Smith D., Griffin J. F. Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor. Science. 1978 Mar 17;199(4334):1214–1216. doi: 10.1126/science.204006. [DOI] [PubMed] [Google Scholar]
  19. Tourwé D., Verschueren K., Frycia A., Davis P., Porreca F., Hruby V. J., Toth G., Jaspers H., Verheyden P., Van Binst G. Conformational restriction of Tyr and Phe side chains in opioid peptides: information about preferred and bioactive side-chain topology. Biopolymers. 1996 Jan;38(1):1–12. doi: 10.1002/(sici)1097-0282(199601)38:1<1::aid-bip1>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  20. Wesson L., Eisenberg D. Atomic solvation parameters applied to molecular dynamics of proteins in solution. Protein Sci. 1992 Feb;1(2):227–235. doi: 10.1002/pro.5560010204. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES