Script for modeling of loops

The new loop optimization method relies on a scoring function and optimization schedule adapted for loop modeling [Fiser et al., 2000]. The corresponding TOP routine is called when you set DO_LOOPS to 1.

The method first takes the generated model, and selects all regions around gaps in the alignment for additional loop modeling. (To select a different region for modeling, simply redefine the select_loop_atoms routine.) An initial loop conformation is then generated by simply positioning the atoms of the loop with uniform spacing on the line that connects the main-chain carbonyl oxygen and amide nitrogen atoms of the N- and C-terminal anchor regions respectively, and this model is written out to a file with the .IL extension.

Next, a number of loop models are generated from LOOP_STARTING_MODEL to LOOP_ENDING_MODEL. Each takes the initial loop conformation and randomizes it by $\pm 5\mbox{\AA}$ in each of the Cartesian directions. The model is then optimized thoroughly twice, firstly considering only the loop atoms and secondly with these atoms ``feeling'' the rest of the system. The loop optimization relies on an atomistic distance-dependent statistical potential of mean force for nonbond interactions [Melo & Feytmans, 1997]. This classifies all amino acid atoms into one of 40 atom classes (as defined in $LIB/atmcls-melo.lib) and applies a potential as MODELLER cubic spline restraints (as defined in $LIB/melo-dist1.lib). Each loop model is written out with the .BL extension.

For more information, please consult the loop modeling paper [Fiser et al., 2000] or look at the loop modeling script itself, __ loop.top.

Example:

# Homology modelling by the MODELLER TOP routine 'model'.
#
# This can be ran with run_clustor model-loop.top, too.
#
# In addition to the standard overall homology modeling, at the end, this 
# routine also calls the thorough loop optimization routine, which generates
# by default 25 loop models for each *.B9999???? model. The default
# loop selection (regions around gaps) can be changed by re-defining 
# routine select_loop_atoms.

INCLUDE                             # Include the predefined TOP routines

SET OUTPUT_CONTROL = 1 1 1 1 0

SET ALNFILE  = 'alignment.ali'      # alignment filename
SET KNOWNS   = '5fd1'               # codes of the templates
SET SEQUENCE = '1fdx'               # code of the target
SET ATOM_FILES_DIRECTORY = './:../atom_files' # directories for input atom files
# SET STARTING_MODEL= 1
# SET ENDING_MODEL  = 1
                                    # (determines how many models to calculate)

SET DO_LOOPS = 1                    # do loops extensively
SET LOOP_STARTING_MODEL = 1
SET LOOP_ENDING_MODEL = 4
SET LOOP_MD_LEVEL = 'refine_1'
SET MD_LEVEL = 'nothing'

CALL ROUTINE = 'model'              # do homology modelling