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Documentation for RosettaVIP Void Indentification and Packing application
Author
Jim Havranek

Metadata

Feb. 2012 by Jim Havranek (havranek [at] genetics.wustl.edu).

Code and Demo

This code uses the RosettaHoles approach to identify problematic buried cavities, and suggests a set of mutations that are predicted to improve stability as determined by improves RosettaHoles and Rosetta fullatom energy scores. The central code is in the vip application in src/protocols/vip/VIP_Mover.cc and in src/protocols/vip/VIP_Report.cc.

For the full workflow check out:

rosetta_demos/public/vip

For a 'minimal' demo example (that omits the post-mutation relaxation step), see

rosetta_tests/integration/tests/vip/

References

Borgo, B., Havranek, J.J. (2012), "Automated selection of stabilizing mutations in designed and natural proteins", Proc. Natl. Acad. Sci. USA, v.109(5) pp.1494-99.

New_Library contains code for this purpose

This code is intended to take a pdb file with the coordinates for a structural model of a protein with poor hydrophobic packing, and to return a list of mutations that are predicted to fill cavities in the protein core. This has been found to result in improved chemical and thermal stability.

Algorithm

This application implements an iterative cycle with three steps. First, cavities and neighboring residue positions are identified. Second, at each of these positions, a single-site design of hydrophobic residues is performed with a simplified score function that assesses geometric complementarity of each side chain with neighboring cavities. Finally, the most promising mutations are imposed in silico, structural relaxtion is performed, and the best mutation as judged by the Rosetta fullatom score function is retained (unless no favorable mutations are identified). This procedure is repeated until no cavities are found, or no new beneficial mutations are identified.

Limitations

Modes

There is only one mode to run the vip application at present.

Input Files

You only need a pdb file of the structure for which you desire suggested mutations, passed to the executable with the -s commandline option described below.

Options

Command Line

The app can be run as follows:

Expected Outputs

The accepted mutations are printed to standard output. A structural model containing all accepted mutations is output as specified by the -cp:output option. If requested by the -cp:print_reports options, a file title "reports.txt" is output that lists the mutations that were found during the single-site design step and the relaxation step, which the improvements in scoring functions noted for each. If requested by the -cp:print_intermediate_pdbs option, a pdb will be printed after each traversal of the iterative cycle.

New things since last release

This application is new as of Rosetta 3.4.