[gmx-users] enegry minimisation

Justin A. Lemkul jalemkul at vt.edu
Wed May 19 16:07:48 CEST 2010



sonali dhindwal wrote:
> Thanks Justin for your help
> I checked the mdout.mpd, all the parameters were interpereted correctly, 
> though from next time i will take care of putting space.
> regarding you asked if those are small molecules, yes those are the 
> ligands and i have taken .itp and .gro file from Dundee Prodrg server. I 
> think those are acceptable !!

I seem to say this several times per week: in my experience (and in the 
experience of many others who have posted here) the charges and charge groups 
output by PRODRG are often unsatisfactory, requiring manual modification and 
validation that they are correct.  This should be absolutely requisite for any 
study involving non-standard small molecules.  Increasingly, I see poor 
parameters used in the literature and it always makes me wonder how the 
simulations can be regarded as valid.  There should be no shortcuts - 
parameterization of small molecules is an advanced topic, requiring great care 
and understanding of the underlying force field.

http://www.gromacs.org/Documentation/How-tos/Parameterization

I don't mean to undermine PRODRG entirely - it is a very useful tool for 
generating a framework topology.  But I have yet to see a topology it produced 
that is at all consistent with the parameters in the Gromos96 force field.  Try 
it yourself - run a known species (like an amino acid) through PRODRG.  The 
results it gives are usually wildly inconsistent with the force field parameter 
library.

-Justin

> Thermostat setup:
> I will now do this thing seperately as protein and non protein only as 
> given in manual.
> 
> And also I will do that thing suggested by Gaurav, hopefully it will 
> help in not distorting the protein structure.
> Thanks a lot.
> 
> --
> Sonali Dhindwal
> 
> 
> --- On *Wed, 19/5/10, Justin A. Lemkul /<jalemkul at vt.edu>/* wrote:
> 
> 
>     From: Justin A. Lemkul <jalemkul at vt.edu>
>     Subject: Re: [gmx-users] enegry minimisation
>     To: "Gromacs Users' List" <gmx-users at gromacs.org>
>     Date: Wednesday, 19 May, 2010, 5:45 PM
> 
> 
> 
>     sonali dhindwal wrote:
>      > Thanks Justin for your reply.
>      > Yes I have included solvent in the protein using genbox.
> 
>     Then you should do energy minimization after constructing the system.
> 
>      > I am pasting .mdp file which I used for MD simulation :
>      >
>      > title               = trp_drg MD
>      > cpp                 = /lib/cpp ; location of cpp on SGI
>      > constraints         = all-bonds
>      > integrator          = md
>      > dt                  = 0.002 ; ps !
>      > nsteps              = 500000 ; total 1 ns.
>      > nstcomm             =1
> 
>     I don't know if this matters or not, but I think your parameters and
>     values should be separated from the '=' by whitespace.  I also don't
>     know if that will have any effect on your unstable system (see
>     below), but do check to make sure that all of your settings have
>     been interpreted correctly.  Confirm your input settings with the
>     mdout.mdp file produced by grompp.
> 
>      > nstxout             = 500 ; output coordinates every 1.0 ps
>      > nstvout             =0
>      > nstfout             =0
>      > nstlist             = 5
>      > ns_type             = grid
>      > rlist               = 0.9
>      > coulombtype         = PME
>      > rcoulomb            = 0.9
>      > rvdw                = 1.4
>      > fourierspacing      = 0.12
>      > fourier_nx        =0
>      > fourier_ny        =0
>      > fourier_nz        =0
>      > pme_order         =6
>      > ewald_rtol        = 1e-5
>      > optimize_fft      = yes
>      > ; Berendsen temperature coupling is on in four groups
>      > Tcoupl                = berendsen
>      > tau_t               = 0.1        0.1   0.1   0.1   0.1   0.1
>      > tc_grps             = Protein    SOL    MG   PEP   E4P   NA+
>      > ref_t               = 300        300   300   300   300   300
> 
>     This thermostat setup is certainly incorrect.  You should not couple
>     all the components of your system to separate thermostats.  See here:
> 
>     http://www.gromacs.org/Documentation/Terminology/Thermostats
> 
>     You have a fairly complicated system.  Are some of these species
>     small molecules?  If so, how did you derive their parameters?  Have
>     you demonstrated that these parameters are accurate?  Which
>     structure is falling apart, and how are you making that assessment?
> 
>     -Justin
> 
>      > ; Pressure coupling is on
>      > Pcoupl              = berendsen
>      > pcoupltype          = isotropic
>      > tau_p               = 0.5
>      > compressibility     = 4.5e-5
>      > ref_p               = 1.0
>      > ; Generate velocites is on at 300 K.
>      > gen_vel             = yes
>      > gen_temp = 300.0
>      > gen_seed = 173529
>      >
>      > I hope it will help you to guide me futher.
>      > Thanks
>      >
>      > --
>      > Sonali Dhindwal
>      >
>      >
>      > --- On *Wed, 19/5/10, Justin A. Lemkul /<jalemkul at vt.edu>/* wrote:
>      >
>      >
>      >     From: Justin A. Lemkul <jalemkul at vt.edu>
>      >     Subject: Re: [gmx-users] enegry minimisation
>      >     To: "Discussion list for GROMACS users" <gmx-users at gromacs.org>
>      >     Date: Wednesday, 19 May, 2010, 5:17 PM
>      >
>      >
>      >
>      >     sonali dhindwal wrote:
>      >      > Hello All
>      >      > This question may sound trivial to many, but as i am new
>     to this
>      >     field, please help.
>      >      > I want to ask a question regarding my previous query of
>      >     distortion of protein strucutre after molecular dynamcs
>     simulation.
>      >
>      >     Can you provide a link to your previous post, for reference?
>      >
>      >      > I have noticed that after enegry minimisation using steepest
>      >     decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 .
>      >      > So is it necessary to do enegry minimisation step before MD,
>      >     because this is my modeled protein, and i have  already done
>     energy
>      >     minimisation using different program and after that I have done
>      >     refinement also.
>      >
>      >     Have you added solvent or anything else to the protein model?  If
>      >     so, then the answer is yes.  Solvation with a regularly-ordered
>      >     lattice of solvent molecules can (and often does) lead to bad
>      >     clashes with your protein structure, thus necessitating further
>      >     minimization.
>      >
>      >     There are plenty of reasons why a protein structure might be
>      >     unstable, most of them related to .mdp file settings, but you
>      >     haven't posted those so there's no way to know if you're doing
>      >     things correctly.
>      >
>      >     -Justin
>      >
>      >      > Thanks and regards
>      >      > ^
>      >      >
>      >      > --
>      >      > Sonali Dhindwal
>      >      >
>      >      >
>      >
>      >     -- ========================================
>      >
>      >     Justin A. Lemkul
>      >     Ph.D. Candidate
>      >     ICTAS Doctoral Scholar
>      >     MILES-IGERT Trainee
>      >     Department of Biochemistry
>      >     Virginia Tech
>      >     Blacksburg, VA
>      >     jalemkul[at]vt.edu | (540) 231-9080
>      >     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>      >
>      >     ========================================
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> 
>     -- ========================================
> 
>     Justin A. Lemkul
>     Ph.D. Candidate
>     ICTAS Doctoral Scholar
>     MILES-IGERT Trainee
>     Department of Biochemistry
>     Virginia Tech
>     Blacksburg, VA
>     jalemkul[at]vt.edu | (540) 231-9080
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
>     ========================================
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> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================



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