[modeller_usage] [Fwd: How to optimize & refine the conformation of the mutant side chain along with the backbone by using modeller (mutate_model.py ) ?]

["Mahesh Velusamy" <>]

Dear All,

I hope you all know that there is script available  in modeller
"mutate_model.py". To generate a mutant models and then optimize the
mutated residue following refinement in sidechain alone but I want to make
this process (optimization/refinement) including the backbone/near
residues instead of restricting only with sidechain.

So, Does anyone know how to modify the default script

I hope the modification needs on the following lines (139 to 153)

#only optimize the selected residue (in first pass, just atoms in selected
#residue, in second pass, include nonbonded neighboring atoms)
#set up the mutate residue selection segment
#s = selection(mdl1.chains[chain].residues[respos])
s = selection(mdl1.chains[chain].residues[respos])

mdl1.restraints.unpick_all()
mdl1.restraints.pick(s)

s.energy()

s.randomize_xyz(deviation=4.0)

mdl1.env.edat.nonbonded_sel_atoms=2
optimize(s,sched)

Thanking you in advance

import sys
import os

from modeller import *
from modeller.optimizers import molecular_dynamics, conjugate_gradients
from modeller.automodel import autosched

#
#  mutate_model.py
#
#     Usage:   python mutate_model.py modelname respos resname chain > logfile
#
#     Example: python mutate_model.py 1t29 1699 LEU A > 1t29.log
#
#
#  Creates a single in silico point mutation to sidechain type and at residue position
#  input by the user, in the structure whose file is modelname.pdb
#  The conformation of the mutant sidechain is optimized by conjugate gradient and
#  refined using some MD.
#
#  Note: if the model has no chain identifier, specify "" for the chain argument.
#


def optimize(atmsel, sched):
    #conjugate gradient
    for step in sched:
        step.optimize(atmsel, max_iterations=200, min_atom_shift=0.001)
    #md
    refine(atmsel)
    cg = conjugate_gradients()
    cg.optimize(atmsel, max_iterations=200, min_atom_shift=0.001)


#molecular dynamics
def refine(atmsel):
    # at T=1000, max_atom_shift for 4fs is cca 0.15 A.
    md = molecular_dynamics(cap_atom_shift=0.39, md_time_step=4.0,
                            md_return='FINAL')
    init_vel = True
    for (its, equil, temps) in ((200, 20, (150.0, 250.0, 400.0, 700.0, 1000.0)),
                                (200, 600,
                                 (1000.0, 800.0, 600.0, 500.0, 400.0, 300.0))):
        for temp in temps:
            md.optimize(atmsel, init_velocities=init_vel, temperature=temp,
                         max_iterations=its, equilibrate=equil)
            init_vel = False


#use homologs and dihedral library for dihedral angle restraints
def make_restraints(mdl1, aln):
   rsr = mdl1.restraints
   rsr.clear()
   s = selection(mdl1)
   for typ in ('stereo', 'phi-psi_binormal'):
       rsr.make(s, restraint_type=typ, aln=aln, spline_on_site=True)
   for typ in ('omega', 'chi1', 'chi2', 'chi3', 'chi4'):
       rsr.make(s, restraint_type=typ+'_dihedral', spline_range=4.0,
                spline_dx=0.3, spline_min_points = 5, aln=aln,
                spline_on_site=True)

#first argument
modelname, respos, restyp, chain,pdb_filename, out_name = sys.argv[1:]


log.verbose()

# Set a different value for rand_seed to get a different final model
env = environ(rand_seed=-49837)

env.io.hetatm = True
#soft sphere potential
env.edat.dynamic_sphere=False
#lennard-jones potential (more accurate)
env.edat.dynamic_lennard=True
env.edat.contact_shell = 4.0
env.edat.update_dynamic = 0.39

# Read customized topology file with phosphoserines (or standard one)
env.libs.topology.read(file='$(LIB)/top_heav.lib')

# Read customized CHARMM parameter library with phosphoserines (or standard one)
env.libs.parameters.read(file='$(LIB)/par.lib')


# Read the original PDB file and copy its sequence to the alignment array:
mdl1 = model(env, file=pdb_filename)
ali = alignment(env)
ali.append_model(mdl1, atom_files=pdb_filename, align_codes=modelname)

#set up the mutate residue selection segment
s = selection(mdl1.chains[chain].residues[respos])

#perform the mutate residue operation
s.mutate(residue_type=restyp)
#get two copies of the sequence.  A modeller trick to get things set up
ali.append_model(mdl1, align_codes=modelname)

# Generate molecular topology for mutant
mdl1.clear_topology()
mdl1.generate_topology(ali[-1])


# Transfer all the coordinates you can from the template native structure
# to the mutant (this works even if the order of atoms in the native PDB
# file is not standard):
#here we are generating the model by reading the template coordinates
mdl1.transfer_xyz(ali)

# Build the remaining unknown coordinates
mdl1.build(initialize_xyz=False, build_method='INTERNAL_COORDINATES')

#yes model2 is the same file as model1.  It's a modeller trick.
mdl2 = model(env, file=pdb_filename)

#required to do a transfer_res_numb
#ali.append_model(mdl2, atom_files=modelname, align_codes=modelname)
#transfers from "model 2" to "model 1"
mdl1.res_num_from(mdl2,ali)

#It is usually necessary to write the mutated sequence out and read it in
#before proceeding, because not all sequence related information about MODEL
#is changed by this command (e.g., internal coordinates, charges, and atom
#types and radii are not updated).

mdl1.write(file=modelname+restyp+respos+chain+'.tmp')
mdl1.read(file=modelname+restyp+respos+chain+'.tmp')

#set up restraints before computing energy
#we do this a second time because the model has been written out and read in,
#clearing the previously set restraints
make_restraints(mdl1, ali)

#a non-bonded pair has to have at least as many selected atoms
mdl1.env.edat.nonbonded_sel_atoms=1

sched = autosched.loop.make_for_model(mdl1)

#only optimize the selected residue (in first pass, just atoms in selected
#residue, in second pass, include nonbonded neighboring atoms)
#set up the mutate residue selection segment
s = selection(mdl1.chains[chain].residues[respos])

mdl1.restraints.unpick_all()
mdl1.restraints.pick(s)

s.energy()

s.randomize_xyz(deviation=4.0)

mdl1.env.edat.nonbonded_sel_atoms=2
optimize(s, sched)

#feels environment (energy computed on pairs that have at least one member
#in the selected)
mdl1.env.edat.nonbonded_sel_atoms=1
optimize(s, sched)

s.energy()

#give a proper name
mdl1.write(file=out_name)

#delete the temporary file
os.remove(modelname+restyp+respos+chain+'.tmp')