Skip to main content

Molecular dynamics simulation of human interleukin-4: comparison with NMR data and effect of pH, counterions and force field on tertiary structure stability

Journal Article


Download full-text (Open Access)

Abstract


  • The human protein interleukin-4 (IL-4) has been simulated at two different pH values 2 and 6, with different amounts of counterions present in the aqueous solution, and with two different force-field parameter sets using molecular dynamics simulation with the aim of validation of force field and simulation set-up by comparison to experimental nuclear magnetic resonance data, such as proton–proton nuclear Overhauser effect (NOE) distance bounds, 3 J(HN,HCα) coupling constants and backbone N–H order parameters. Thirteen simulations varying in the length from 3 to 7 ns are compared.

    At pH 6 both force-field parameter sets used do largely reproduce the NOE's and order parameters, the GROMOS 45A3 set slightly better than the GROMOS 53A6 set. 3 J values predicted from the simulation agree less well with experimental values. At pH 2 the protein unfolds, unless counterions are explicitly present in the system, but even then the agreement with experiment is worse than at pH 6. When simulating a highly charged protein, such as IL-4 at pH 2, the inclusion of counterions in the simulation seems mandatory.

Authors


  •   Winger, Mortiz (external author)
  •   Yu, Haibo
  •   Redfield, Christina (external author)
  •   van Gunsteren, Wilfred (external author)

Publication Date


  • 2007

Citation


  • Winger, M., Yu, H., Redfield, C. & van Gunsteren, W. F. (2007). Molecular dynamics simulation of human interleukin-4: comparison with NMR data and effect of pH, counterions and force field on tertiary structure stability. Molecular Simulation, 33 (14), 1143-1154.

Scopus Eid


  • 2-s2.0-36949031938

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1883&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/844

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1143

End Page


  • 1154

Volume


  • 33

Issue


  • 14

Abstract


  • The human protein interleukin-4 (IL-4) has been simulated at two different pH values 2 and 6, with different amounts of counterions present in the aqueous solution, and with two different force-field parameter sets using molecular dynamics simulation with the aim of validation of force field and simulation set-up by comparison to experimental nuclear magnetic resonance data, such as proton–proton nuclear Overhauser effect (NOE) distance bounds, 3 J(HN,HCα) coupling constants and backbone N–H order parameters. Thirteen simulations varying in the length from 3 to 7 ns are compared.

    At pH 6 both force-field parameter sets used do largely reproduce the NOE's and order parameters, the GROMOS 45A3 set slightly better than the GROMOS 53A6 set. 3 J values predicted from the simulation agree less well with experimental values. At pH 2 the protein unfolds, unless counterions are explicitly present in the system, but even then the agreement with experiment is worse than at pH 6. When simulating a highly charged protein, such as IL-4 at pH 2, the inclusion of counterions in the simulation seems mandatory.

Authors


  •   Winger, Mortiz (external author)
  •   Yu, Haibo
  •   Redfield, Christina (external author)
  •   van Gunsteren, Wilfred (external author)

Publication Date


  • 2007

Citation


  • Winger, M., Yu, H., Redfield, C. & van Gunsteren, W. F. (2007). Molecular dynamics simulation of human interleukin-4: comparison with NMR data and effect of pH, counterions and force field on tertiary structure stability. Molecular Simulation, 33 (14), 1143-1154.

Scopus Eid


  • 2-s2.0-36949031938

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1883&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/844

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1143

End Page


  • 1154

Volume


  • 33

Issue


  • 14