Molecular dynamics simulation of human interleukin-4: comparison with NMR data and effect of pH,counterions and force field on tertiary structure stability |
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| Authors: | M. Winger H. Yu C. Redfield |
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| Affiliation: | 1. Laboratory of Physical Chemistry , Swiss Federal Institute of Technology Zürich, ETH , 8093, Zürich, Switzerland;2. Department of Chemistry , University of Wisconsin-Madison , 1101 University Avenue, Madison, WI, 53706, USA;3. Department of Biochemistry , University of Oxford , South Parks Road, Oxford, OX1 3QU, UK |
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| 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. |
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| Keywords: | Interleukin-4 Low pH Unfolding Molecular dynamics simulation Counterions |
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