Simulations of chemical exchange in NMR

using QSim QSim

Magnus Helgstrand, PhD
Dept. of Biophysical Chemistry, Lund University, Box 124, SE-221 00 Lund, Sweden (magnus.helgstrand@bpc.lu.se)

Chemical exchange processes in proteins on the millisecond timescale is an area well suited for study by NMR.
Processes of interest include protein folding, enzyme kinetics and ligand binding.
We have used the NMR simulation program QSim1 to simulate chemical exchange processes in NMR. QSim is a
program that numerically simulates NMR pulse sequences with high accuracy, using a quantum mechanical de-
scription. QSim uses Cartesian product operators as a basis and includes relaxation and chemical exchange during
the entire pulse sequence. QSim has a graphical user interface and is thus easy to use.
Chemical exchange processes typical for proteins, including two and three state chemical exchange, SQ, ZQ and
DQ CPMG experiments2-6 are simulated. ZQ and DQ can not be simulated using a classical mechanics approach,
and are thus ideal to simulate with QSim. Relaxation dispersion curves for different chemical exchange schemes
and CPMG experiments are plotted.

Method
1. Construct pulse sequence 2. Define spin system 3. Perform simulation

Results
Conclusion
1st state k12 = 20 s-1 2nd state k23 = 600 s-1 3d state
We believe that simulating chemical exchange experiments is an easy, fast and accurate
ΩH = 0 Hz ΩH = 600 Hz ΩH = -100 Hz
k21 = 400 s-1 k32 = 50 s-1
way to test different chemical exchange models. The results of simulations will then aid the
ΩN = 200 Hz ΩN = 0 Hz ΩN = -50 Hz
NMR spectroscopist in designing and running suitable experiments to discard or confirm
specific chemical exchange models in real biological systems.
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15
N SQ 1
H SQ
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25,00 25,00 QSim References

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QSim is constructed by Magnus Helgstrand and Peter Allard and can be 1. Helgstrand, M. and P. Al-
downloaded from http://www.bpc.lu.se/QSim. QSim is free to use after lard (2004) J. Biomol. NMR.
registration.
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1
H-15N ZQ 1
H-15N DQ 2. Meiboom, S. and D. Gill
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(1958) Rev. Sci. Instrum. 29,
25,00 25,00 Main features: 688-691.
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• Accurate simulations • Pulsed field gradients 3. Carr, H.Y. and E.M. Pur-
cell (1954) Phys. Rev. 94, 630-
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• Graphical user interface • Watches
638.
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• Classical or QM simulations • Custom start magnetization
4. Ishima, R. and D.A. Tor-
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• Any spin quantum number • Effective Liouvillians chia (2003) J. Biomol. NMR.
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0 200 400 600 800 1000 1200 1400 1600 1800 2000
• Residual dipolar couplings • Spectra processed in program 25, 243-248
• Residual quadrupolar couplings • Spectra viewed in program 5. Loria, J.P., Rance M. and
Simulations of different CPMG experiments2-6 as indicated. Relaxation rates are plotted as function of • Relaxation interference effects • Stand-alone simulation classes A.G. Palmer 3rd. (1999) J. Bio-
CPMG frequency. The spin system consisted of an 1H-15N entity with dHN = 1.02 Å and JHN = -92 Hz. • Chemical exchange • Runs on desktop PCs mol. NMR. 15, 151-155
Modelfree parameters were set to: τm = 25 ns, τe = 50 ps and S2 = 0.8. Chemical shifts and exchange 6. Orekhov V.Y., Korzhnev
• Graphical pulse sequences • Results can be exported
rates as indicated above. Diamonds denote simulations without chemical exchange, squares two-state D.M. and L.E. Kay (2004) J.
chemical exchange and triangles three-state chemical exchange. • Decoupling sequences • Free for everyone to use
Am. Chem. Soc. 126, 1886-
• Shaped pulses 1891