Virtual NMR Spectrometer a software package for accurate and efficient calculation of the outcome of

1
Virtual NMR Spectrometer a software package for
accurate andefficient calculation of the outcome
of NMR experiments and a computer tool for
learning NMR

• David Fushman
• Department of Chemistry Biochemistry
• University of Maryland, College Park

2
Why do we need computer simulations in NMR?

• 3D CT-HN(CA)CB, Shan et al., 1996, JACS 118, 6570

3
Why do we need computer simulations in NMR?

• ? Modern multidimensional NMR experiments involve
  pulse-field gradients, shaped RF pulses,
  off-resonance effects, complex decoupling
  schemes, and much more
• it has become practically impossible to
  accurately predict the outcome
• of these complicated pulse sequences under
  real conditions
• ? We need to be able to optimize experimental
  conditions with minimal cost of NMR time
  (especially for 3D, 4D expts)
• ? We need efficient tools for designing new pulse
  sequences (especially for multidimensional expts)
• ? Learning NMR -- Difficulties in understanding
  theoretical aspects of NMR
• Practical aspects insufficient access to NMR
  instruments

4
Real experimental conditions can be far from
ideal conditions
We have theoretical approaches that allow us to
accurately predict the outcome of many NMR
experiments under ideal conditions, but

• Pulse imperfectionsOff-resonance effectsSpin
  relaxationExchange phenomena Water suppression
  etc

5
VNMR The Virtual NMR Spectrometer
Introducing

• A NMR spectrometer that you can carry in your bag

6
VNMR The Virtual NMR Spectrometer Flowchart
of the Virtual Spectrometer
Experimental or user-designed pulse sequence
TRANSLATOR
SIMULATOR NMR Experiment Preparation ?
Evolution ? Data Acquisition
DATA PROCESSING 1D or nD Spectra
Experimental Conditions Spin System Setup
Input
Output
Calculation
7
VNMR Treatment of spin evolution

• Spin Hamiltonian in the rotating frame

Spin Density Evolution
Spin Relaxation, Cross-relaxation, Chem.Exchange
etc
8
VNMR Basic Goals

• Accuracy and efficiency in simulation of various
  pulse sequences, including PFG and shaped RF
  pulses
• The ability to execute the actual pulse sequences
  from the spectrometer
• Ease of use (intuitive GUI, no programming
  skills, OS/platform independence)
• Flexibility in selecting various spin systems and
  experimental conditions
• Tools for data processing, analysis, and
  visualization

9
VNMR 3.1 (pre-beta) Highlight of Basic Features

• 1D, 2D, almost finished 3D
• Translator (Bruker ? VNMR) allows running
  actual pulse sequences
• Simulation of various pulse sequences, including
  PFG and shaped RF pulses
• Data processing, analysis, and visualization of
  the results
• Shaped pulse generator
• Tracing/visualization of spin-density components
• Relaxation calculator
• Save/load capabilities
• Converters to basic NMR processing packages
  XWINNMR, (nmrPIPE)
• Experimental noise

10
Virtual NMR Spectrometer a tool for in silico
NMR
11
A simple example COSY
3-spin system
Jab 20 Hz Jab 12 Hz Jbb 30 Hz
Ha 4.2 ppm Hb 2.8 ppm Hb 3.3 ppm
12
A simple example Homonuclear COSY

• Suppression of the axial noise

ns 1
ns 8
13
Another example DQF COSY

• 3-spin DQF COSY

14
DQF COSY
15
NMR Experiments Involving Pulsed Field Gradients

• Next example Gradient-selective COSY (cosygs)

How to treat gradients accurately?
16
Gradient treatment Salami model
NMR Experiments Involving Pulsed Field Gradients
17
Gradient treatment flowchart
Initialization Calculate Ba, Hevol, R Initialize
spin density s1 seq
Set i 1 GRADoff
Calculate Hi, si1 Increment i
N
GRADon ?
Y
CTP
Salami
Split si into NL layers


For each layer nz Calculate Hi(nz), si1(nz)
Store si1(nz) Increment i
Calculate Hi , si1 Calculate T, then wi, ki
Increment i
End of pulse sequence?
End of pulse sequence?
N
N
Y
Y
Average s
Integrate s
Acquisition
Increment ns and phases
N
ns gt NS ?
Y
Stop
18
Gradient selection of P- or N- type coherences
or both
19
Another example -- decoupled 1H-15N HSQC
20
Closer to reality differential line broadening
21
Relaxation calculator

• In order to reconstruct the actual experimental
  conditions, we need to be able to use
  spin-relaxation parameters as close as possible
  to the reality

22
Coupled 1H-15N HSQC
23
1H-15N HSQC coupled/decoupled

• Now with differential line widths

24
Projections displayallows tracking of
user-selected components of the spin density in
the course of NMR experiment, for testing and
educational purposes

• HSQC example

25
TROSYsimulation
26
Transverse-Relaxation Optimized SpectroscopY
(TROSY)

• Using the interference between Dipolar
  interaction and CSA

27
Virtual Spectrometer Web Site
www.vsnmr.org

• Coming soon
• Beta-testing version
• Demo versions for students

28
VNMR as NMR learning tool

• Easiness of use and broad accessibility
• It does not require programming skills
• Even more so -- you dont need a spectrometer!!!
• Intuitive User Interface
• Compatibility with Bruker programming
  language
• Future plans Web access
• Demo versions
• Set of basic NMR experiments

29
Acknowledgements

• David Cowburn (Rockefeller U.)
• Vlad Ruchinsky (Yale U.)
• Peter Nicholas (UNC Medical School)
• Konstantin Berlin (U.Maryland)
• Grant Support
• Camille Henry Dreyfus Foundation
• National Science Foundation