FastContact 2.0

a free energy scoring tool for protein-protein complex structures

Contents 1 Usage 1.1 Required user-input information 1.2 Optional parameters 1.3 Output format and explanation 2 Keywords 3 See also 4 References 4.1 Further reading 5 External links

Usage

Required user-input information

The user uploads two Protein Data Bank (PDB) format files, one 'receptor' and one 'ligand', along with their email address. The web server currently makes no distinction between chains; it simply reads in each line in the PDB file starting with an 'ATOM' field. The maximum number of residues is limited to 1500. The email address is where the output/results will be sent (as a file attachment). Hydrogen bonds and missing atoms are built and optimized on the uploaded structures using the molecular software CHARMm.

Optional parameters

Range of desolvation interaction: The default range is 6 Å, such that the potential smoothly goes to zero between 5 and 7 Å. This range is suggested for refined models, without overlaps and relatively snug interfaces. The user has the option of changing the range to 9 Å, approaching 0 between 8 and 10 Å. This modality is suggested for encounter complexes.

Minimization: The default setting for Hydrogen bond optimization and removal of minimal overlaps prescribes a short 3x20 ABNR minimization steps with fixed backbone using the program CHARMm and the PARAM19 Residue Topology File (RTF). However, the user is free to change this setting to a full atom minimization. This setting will work for single chains only and no gaps.

Patch end terminals with -NH3+ and -COOH: By default, the end terminal residues will be patched by CHARMm. In case the end terminals are missing from the structure, the user has the option of turning the patching feature off.

Output format and explanation

The results from a FastContact server run are returned to the user via email as a file attachment (with a normal response time of about one minute). The attached file is a gzipped archive (.tar.gz) containing three results files: (a) the main results file ('output.txt'); and, the processed (including H-bonds) (b) receptor PDB file and (c) the ligand PDB file. All of the files are prefixed with the user name (email prefix) and timestamp of the server run for easy reference.

The main results file ('output.txt') returns two components of a free energy function, electrostatic energy and desolvation free energy, and evaluates the solute the van der Waals energy using CHARMm. The latter is sometimes useful to compare between different models, but here it is given only as a reference since it is not used in the analysis of contacts. Often vdW energies larger than about -500 kcal/mol suggest structural overlaps. Although FastContact smooths the potentials to tolerate some limited overlaps, these are, in general, detrimental to the quality of the computational estimates.

Keywords

PDB, docking, free energy scoring, contact potential, binding free energy, protein interactions, complex structure, binding mechanism, recognition, desolvation

References

1. ↑ ^1.1 1.2 Camacho CJ and Zhang C (2005). FastContact: rapid estimate of contact and binding free energies. Bioinformatics, 21(10):2534-6.

Further reading

• Champ PC and Camacho CJ (2007). FastContact: a free energy scoring tool for protein-protein complex structures. Nucleic Acids Res. (Web addition).
• Camacho CJ, Ma H, and Champ PC (2006). Scoring a diverse set of high-quality docked conformations: A metascore based on electrostatic and desolvation interactions. Proteins, 63(4):868-77.

External links

• FastContact Server
• FastContact binaries — available for download
• FastContact wiki

<< Back to Server

• Reference: Camacho CJ and Zhang C (2005). FastContact: rapid estimate of contact and binding free energies. Bioinformatics, 21(10):2534-6.
• This server was setup by
  P. Christoph Champ
  in July 2005 at the University of Pittsburgh.
• "This material is based upon work supported by the National Science Foundation under Grant No. 0444291."
  "Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation."