Contents

• Contents
• Motivation
• Features of program
• Accurate site-specific fits to two-state exchange model at any timescale
• Refinement of best fit for maximum accuracy
• Examine dynamic motion of entire molecule
• Optimization and education with RD Simulator
• Access the power of Matlab
• Online documentation and support
• Download latest version
• Acknowledgements
• Citing GUARDD
• Author

Motivation

• Protein dynamics are essential for life
• NMR dispersion experiments can be used to quantify protein dynamics
• Dispersion experiments are difficult to analyze
• Under-determined – many fitting parameters compared to amount of observed data
• Visual inspection of curve and data does not validate fit accuracy
• Curve fit may go through data points even if parameters are inaccurate
• Dynamics are complex
• Global or local protein motions?
• What is the nature of the dynamic process?
• Unfolding? Exchange towards defined minor state? Conformational selection?
• Currently available RD analysis software does not provide graphical interface nor advanced display options
• Less "black box", more "hands on"

Features of program

• Graphical user interface
• Point-and-click functionality for ease of use

Accurate site-specific fits to two-state exchange model at any timescale

• Global fits of data at multiple temperatures, magnetic fields and quantum coherences
• Carver-Richards formulae describes two-state exchange at any timescale (not fast approximation)
• Statistical comparison of two-state exchange and no-exchange models

Refinement of best fit for maximum accuracy

• Grid search of initial fitting conditions helps identify global minimum of χ²
• Produces plots of χ²-space to determine quality of fit
• User can drive fit towards most reasonable solution
• Ill-defined parameters can be marked to avoid mis-interpretation and maximize extraction of information

Examine dynamic motion of entire molecule

• Group analysis and parameter examiner displays results in novel ways
• Can identify global motions and nature of minor excited state

Optimization and education with RD Simulator

• Explore the nature of RD phenomena to plan future experiments and to enhance understanding of RD
• Export simulated data for subsequent fitting and analysis

Access the power of Matlab

• Utilize Matlab's built-in functionality to help display and interpret your results
• Matlab Central provides a large community for documentation and user support link

Online documentation and support

• Documentation can be read on the Wiki page link
• Issues can be reported and reviewed online link
• Email the author and a community of users for support link

Download latest version

• Check the download section for the latest version link
• Four MATLAB requirements: MATLAB, Optimization Toolbox, Curve Fitting Toolbox, Statistics Toolbox

Acknowledgements

• Foster Lab members for debugging during development
• Advisor Prof. Mark Foster link
• The Ohio State University Biochemistry Dept. link
• The Ohio State University Biophysics Program link
• The Ohio State University link
• National Institutes of Health link

Citing GUARDD

• GUARDD manuscript: http://dx.doi.org/10.1007/s10858-011-9589-y

• Please cite your usage of GUARDD in BOTH ways
1. Kleckner, I. R., & Foster, M. P. (in press). GUARDD: User-friendly MATLAB software for rigorous analysis of CPMG RD NMR data. Journal of Biomolecular NMR. doi: 10.1007/s10858-011-9589-y
2. http://code.google.com/p/guardd/

Author

• (C) Ian Kleckner
• Mark Foster's Lab
• The Ohio State University
• Columbus, OH, USA