Re: [modeller_usage] Is it possible to do single residue optimization for automodels ?

[david gae <>]

Hi Mahesh, 

I’m not an expert in modeler. But, I have carried out some modeling in the past with modeller. 
You can give different random seed number to get different conformation of your point mutation using the mutate_model.py

for example:
 env = environ(rand_seed=-49837)  to env = environ(rand_seed=200)  

By the way, I dont follow your logic when you say "there is not much variations”. For example, when you make changes to a surface residue you may get different side chain orientation, but if you have a buried residue surround by side chains, I believe you won’t get much changes as well as the size and charge will play a factor here. 

All the best, 
David 



> On Jun 27, 2016, at 8:08 AM, Mahesh Velusamy <> wrote:
> 
> Dear All,
> 
> Since, My main objective is to get a better conformational sample for a
> particular single point mutation, I have generated a 100 number of SPM
> models through automodel but Since, Automodel uses the distance restraints
> from the template target structure alignment there is not much variations
> when comparing with the original structure.  So I thought to relax the
> restrains by doing additional optimization on mutated position alone like
> we see in mutate_model.py http://salilab.org/modeller/wiki/Mutate%20model.
> 
> 
> Then, I try to modified the automodel script as same like mutate_model.py
> but I endup in lot of confusions that
> 
> 1.what shoud I keep for :
>    #conjugate gradient
>    for step in sched:
>        step.optimize(atmsel, max_iterations=200, min_atom_shift=0.001
> 
> 2.Whether should I include make restraints function ?
> 
> 3. Is it Ok If I do only optimize and refine step ?
> 
> 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)
> 
> a = MyModel(env, alnfile=current_file, knowns='3O26', sequence='R1Y',
> assess_methods=(assess.DOPE, assess.GA341))
> a.starting_model = 1
> a.ending_model = 1
> a.make()
> 
> So , Could you guide me on single residue optimization on automodel
> structures ?
> 
> Thanking you in advance
> 
> 
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