1. Rong Chen Boston University
Protein Docking
Rong Chen
Boston University

2. The Lowest Binding Free Energy DG
water L R L R R L R L L R

3. Protein Docking Using FFT
Fast Fourier Transform
Complex
Conjugate
Discretize
Correlation function
Fast Fourier
Transform L L
Rotate L
Discretize
Surface
Interior

4. Rotational Sampling Sampling Interval Number of angles 20° 1,800 15°
Evenly distributed Euler angles
Sampling Interval
Number of angles
20°
1,800
15°
3,600
12°
9,000
10°
14,400 8°
27,000 6°
54,000 4°
180,000

5. Performance Evaluation
Success Rate: given the number of predictions(Np), success rate is the percentage of complexes in the benchmark for which at least one hit has been obtained.
Hit Count: the average number of hits over all complexes at a particular Np.

6. Rotational Sampling Density

7. Rotational Sampling Density

8. Protein Docking Using FFT
Fast Fourier Transform
Complex
Conjugate
Discretize
Correlation function
Fast Fourier
Transform L L
Rotate L
Discretize
Surface
Interior

9. Protein Docking Using FFT
Increase the speed by 107
Y Translation
Correlation
X Translation L R
IFFT
Surface
Interior
Binding Site

10. An Effective Binding Free Energy Function
van der Waals energy; Shape complementarity
Desolvation energy; Hydrophobicity
Electrostatic interaction energy
Translational, rotational and vibrational free energy changes
Number of atom pairs of type i
Desolvation energy for an atom pair of type i

11. Grid-based Shape Complementarity1
RGSC
LGSC

12. Pairwise Shape Complementarity2 3 5 1
RPSC
LPSC

13. PSC vs. GSC on Success Rate

14. PSC vs. GSC on Hit Count

15. Why PSC works better than GSC?

16. Why PSC works better than GSC?D

17. A Receptor-Ligand Complex

18. An Effective Binding Free Energy Function
van der Waals energy; Shape complementarity
Desolvation energy; Hydrophobicity
Electrostatic interaction energy
Translational, rotational and vibrational free energy changes
Number of atom pairs of type i-j
Desolvation energy for an atom pair of type i-j

19. Impact of Desolvation and Electrostatics

20. Impact of Desolvation and Electrostatics

21. Other available Docking Software
Fast Fourier Transform or FFT (Katchalski-Katzir, Sternberg, Vakser, Ten Eyck groups)
Computer vision based method (Nussinov group, 1999)
Boolean operations (Palma et al., 2000)
Polar Fourier correlations (Ritchie & Kemp, 2000)
Genetic algorithm (Gardiner, Burnett groups)
Flexible docking (Abagyan, 2002)

22. 3D-Dock
Michael J.E. Sternberg, Imperial Cancer Research Fund, London, UK.
FTDock: Grid-based shape complementarity, FFT.
RPScore: empirical pair potential.
MultiDock: refinement.

23. GRAMM Ilya A. Vakser, State University of New York at Stony Brook.
Geometric fit and hydrophobicity
FFT
Low resolution docking

24. DOT Lynn F. Ten Eyck, University of California, San Diego.
Grid-based shape complemetarity, elctrostatics
FFT

25. ICM Ruben Abagyan, The Scripps Research Institute, La Jolla.
Pseudo-Brownian rigid-body docking
Biased Probability Monte Carlo Minimization of the ligand interacting side-chains.

26. HEX Dave Ritchie, University of Aberdeen, Aberdeen, Scotland, UK
spherical polar Fourier correlations

27. Approach Overview PDB1 PDB2 PDB Processing Biological information
ZDOCK: Initial-stage Docking
Biological information
RDOCK: Refinement-stage Docking
Clustering
Final 10 predictions

28. Example:
CAPRI Target 6: α-amylase / Camelid VHH domain