Computational prediction of threedimensional protein structure from
NMR chemical shifts
Kai Kohlhoff
Microsoft Research Summer School
Cambridge
July 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
X-ray crystallography
NMR spectroscopy
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Molecular dynamics simulations
E R   Ebond  Eangle  Edihedral  Eelectrostatic  EvdW
Source: http://www.ch.embnet.org/MD_tutorial/
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Free energy surface
Source: http://www.lsbu.ac.uk/water/protein.html#fold
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
NMR chemical shifts
sB0
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
CamShift chemical shift predictor
n
 d
Donor
 calc   rc   bb f bb   sc f sc   nb f nb   ring f ring   hbond f hbond   diheds f diheds  ...
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
E R   Ebond  Eangle  Edihedral  Eelectrostatic  EvdW  ECamShift
Energy
Source: http://www.ch.embnet.org/MD_tutorial/
Cambridge 2008
exp - calc
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Cambridge 2008
Computational prediction of three-dimensional protein structure from NMR chemical shifts
MD
Energy
CamShift-MD
Backbone RMSD (in Å = 0.1 nm)
0.7
Control
Truncated PVO (PDB 1PVO)
Backbone RMSD (nm)
0.6
CamShift-MD
0.5
0.4
0.3
0.2
0.1
0
GSGS
Helix
PVO
Structure
Cambridge 2008
Ubiquitin
GB3
Computational prediction of three-dimensional protein structure from NMR chemical shifts
Acknowledgements
Vendruscolo and Dobson group members
Michele Vendruscolo
Andrea Cavalli
Paul Robustelli
Xavier Salvatella
Gian Gaetano Tartaglia
Joerg Gsponer
Funding
Microsoft Research
Cambridge 2008