SmoothDock
SmoothDock is an algorithm for finding physical interactions between proteins involved in common cellular functions. It was developed by Carlos J. Camacho and Christoph Champ at the University of Pittsburgh. It is based upon a previous algorithm, ClusPro, developed by Camacho and Steven R. Comeau at Boston University (note: ClusPro is also based on a previous algorithm, Consensus).
Contents
The SmoothDock algorithm
The SmoothDock algorithm comprises four steps:
- perform rigid-body docking using the program DOT, keeping the top 20,000 structures as ranked by surface complementarity;
- re-rank these structures according to a free energy estimate that includes both desolvation and electrostatics and retain the top 2,000 complexes;
- cluster the filtered complexes using a pairwise RMS deviation criterion; and
- the twenty-five largest clusters are subject to a smooth docking discrimination algorithm where van der Waals forces are taken into account.
Step 1: rigid-body docking
Rigid-body docking using the Fast-Fourier Transform (FFT) based program DOT[1][2] was performed for each receptor/ligand target. The output of this program was the top 20,000 receptor/ligand complexes sampled by the DOT program and ranked according to surface complementarity. Any experimental constraint on the binding area was also imposed here.
Step 2: filtering decoys
Following the procedure detailed elsewhere[3][4][5], for each complex we computed the effective desolvation and electrostatic binding affinity between receptor and ligand. We then filtered the 500 best desolvation energy[6] and 1,500 best electrostatic energy[7] complexes for a total of 2,000 complex candidates.
Step 3: clustering decoys
We clustered the filtered complexes using a pairwise RMS deviation (RMSD) criterion, and retained the twenty-five clusters with the highest number of neighbors[8].
The complexes are clustered in either of two ways:
- using an all C_α RMSD criterion and a 10 Å cutoff; and
- using a C_α binding site RMSD criterion and a cutoff radius of 7 Å.
All clustering was done in a hierarchical manner such that no overlaps occurred between distinct clusters.
Step 4: refinement and discrimination of native-like clusters
Using 10 representative structures from each cluster, the smooth docking algorithm[9] was used to optimize our free energy function around each cluster. We submitted the top ranked complexes from those clusters that converged to the lowest free energies as estimated by Eq.1:
ΔG = E_elec + E_desolv + E_vdw (Eq.1)
Notes
- low affinity complexes: K_d < nM
See also
References
Citations
- ↑ Ten Eyck LF, Mandell J, Roberts VA, Pique ME (1995). Surveying molecular interactions with DOT. In: Hayes A, Simmons M, editors. Proceedings of the 1995 ACM/IEEE Supercomputing Conference. New York: ACM Press.
- ↑ Katchalski-Katzir E, Shariv I, Eisenstein M, Friesem A, Aflalo C, Vakser I (1992). Molecular surface recognition: determinination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci USA, 89:2195-2199.
- ↑ Camacho C, Gatchell D, Kimura R, Vajda S (2000). Scoring docked conformations generated by rigid body protein-protein docking. Proteins, 40:525-537.
- ↑ Gatchell D, Vajda S, Camacho CJ. Sampling, clustering, refinement and discrimination of protein interactions using SmoothDock. To be Submitted.
- ↑ Camacho CJ, Weng Z, Vajda S, DeLisi C (1999). Free energy landscapes of encounter complexes in protein-protein association. Biophys J, 76:1166-1178.
- ↑ Zhang C, Vasmatzis G, Cornette JL (1997). Determination of atomic desolvation energies from the structures of crystallized proteins. J Mol Biol, 267:707-726.
- ↑ Camacho C, Gatchell D, Kimura R, Vajda S (2000). Scoring docked conformations generated by rigid body protein-protein docking. Proteins, 40:525-537.
- ↑ Gatchell D, Vajda S, Camacho CJ. Sampling, clustering, refinement and discrimination of protein interactions using SmoothDock. To be Submitted.
- ↑ Camacho CJ, Vajda S (2001). Protein docking along smooth association pathways. Proc Natl Acad Sci USA, 98:10636-10641.
