AUTHOR==Sinisa Bjelic and TJ Brunette
METADATA==This document was last updated August 11, 2010 by TJ Brunette & Sinisa Bjelic. The corresponding PIs for this application are David Baker <dbaker@u.washington.edu>.
EXAMPLES==See mini/test/integration/tests/loop_modeling for an example loop relax run and input files.
REFERENCES==Qian, B., Raman, S., Das, R., Bradley, P., McCoy, A.J., Read, R.J. and Baker D. (2007). High resolution protein structure prediction and the crystallographic phase problem. Nature. manuscript accepted.\nWang, C., Bradley, P. and Baker, D. (2007) Protein-protein docking with backbone flexibility. Journal of Molecular Biology, in press, DOI,http://dx.doi.org/10.1016/j.jmb.2007.07.050
DESCRIPTION==Loop modeling is performed by two different algorithms CCD (Cyclic coordinate descent) and KIC (Kinematic closure). Here only CCD is described and the explanation of the latter can be found the corresponding KIC documentation. The goal of both algorithms is to explore the conformational space of the loop using a centroid representation of protein side-chains and explicit backbone representation, followed by a higher-resolution search using explicit representations of all atoms and hydrogen.\n\nThe centroid stage of loop-modeling generates loops by performing fragment insertions using Monte Carlo sampling, a score to reward closed chains, and CCD is used to close the loop at the end of the simulation. As the fragments are necessary for the sampling these have to be generated by fragment picker ( c.f. fragment picker documentation) or downloaded from the Robetta web-server.
INPUTS==Start pdbs: The template pdb file and must have real coordinates for all template residues plus the first and last residue of each loop region.  Loop file (Create using the GUI - check export):
TIPS==For production runs, it is recommended to use the following flags. -loops::remodel quick_ccd -loops::refine refine_kic -loops::relax fastrelax -relax::fastrelax_repeats 8 -loops::extended and to generate at least 1000 models using -nstruct 1000.\nquick_ccd can also remodel termini. To do this set the cutpoint in the loops file to be equal to the last residue in the chain. For example for a 80 residue protein, if you want to remodel the first 10 residues the loop file would have 1 10 10 0 0\nquick_ccd does not require constraints, but using constraints from homologs or experimental data can produce more accurate results. Output consists of a pdb and a scorefile. The job concludes with the following command:\nprotocols.looprelax: ===\nprotocols::checkpoint: Deleting checkpoints of Loopbuild
ANALYSIS==For benchmarking purposes, creating a score vs rmsd plot across decoys and looking for near native 'energy funnels' is good way to test the performance of the protocols on a system, and can help to determine whether errors are due to scoring or sampling. For blind prediction and refinement, such plots can still be useful to look for convergence or multiple minima in the energy landscape. Decoys may also be pairwise-clustered to search for well-populated regions of conformational space that may represent alternative low-energy conformations. (from KIC loopclosure)
