[gmx-users] enegry minimisation

Justin A. Lemkul jalemkul at vt.edu
Thu May 20 15:16:04 CEST 2010



sonali dhindwal wrote:
> Hello Gaurav,
> when i did g_rms with structre before energy minimisation as refrence 
> and strucutre after energy minimisation, it came to be around 0.02.
> 

Is that backbone RMSD or does it consider all protein atoms?  In either case, a 
value of 0.02 indicates a very small amount of change in the protein structure, 
which makes it very hard to believe that any large-scale alteration of the 
secondary structure is happening.

-Justin

> --
> Sonali Dhindwal
> 
> 
> --- On *Thu, 20/5/10, Gaurav Goel /<gauravgoeluta at gmail.com>/* wrote:
> 
> 
>     From: Gaurav Goel <gauravgoeluta at gmail.com>
>     Subject: Re: [gmx-users] enegry minimisation
>     To: jalemkul at vt.edu, "Discussion list for GROMACS users"
>     <gmx-users at gromacs.org>
>     Date: Thursday, 20 May, 2010, 5:36 PM
> 
>     Can you try using g_rms to compare the difference between the
>     structures before and after EM.
> 
>     -Gaurav
> 
>     On Thu, May 20, 2010 at 7:53 AM, Justin A. Lemkul <jalemkul at vt.edu
>     </mc/compose?to=jalemkul at vt.edu>> wrote:
>      >
>      >
>      > sonali dhindwal wrote:
>      >>
>      >> Hello Gaurav,
>      >> Thanks for your reply,
>      >> I did position restrained enegry minimisation, and used
>     following .mdp
>      >> file for the same
>      >>
>      >> title = protein
>      >> cpp = /usr/bin/cpp ; the c pre-processor
>      >> define = -DPOSRE
>      >> constraints = none
>      >> integrator = steep
>      >> dt = 0.002 ; ps !
>      >> nsteps = 1000
>      >> nstlist = 10
>      >> ns_type = grid
>      >> rlist = 0.9
>      >> coulombtype = PME
>      >> rcoulomb = 0.9
>      >> rvdw = 0.9
>      >> fourierspacing = 0.12
>      >> fourier_nx = 0
>      >> fourier_ny = 0
>      >> fourier_nz = 0
>      >> pme_order = 4
>      >> ewald_rtol = 1e-5
>      >> optimize_fft = yes
>      >> ;
>      >> ; Energy minimizing stuff
>      >> ;
>      >> emtol = 1000.0
>      >> emstep = 0.01
>      >> pbc = xyz
>      >>
>      >> I included define = -DPOSRE, for restraining the atom postion,
>      >> I used posre.itp which was genertaed by pdb2gmx.
>      >>
>      >> Have I done it correctly, because after this also many of the
>     beeta sheets
>      >> have become short, forming loops.
>      >
>      > Well, you haven't properly defined position restraints. The default
>      > (produced by pdb2gmx) requires "define = -DPOSRES" not "-DPOSRE."
>     If you
>      > have for some reason modified the topology, then maybe your
>     approach is
>      > correct, but otherwise your position restraints are not being
>     applied.
>      >
>      > I also find it very curious that such substantial changes are
>     taking place
>      > during a simple energy minimization. Are you sure the effects you are
>      > seeing are not simply due to the visualization software you are using
>      > guessing the incorrect secondary structure type? I have had that
>     experience
>      > numerous times, especially in the case of beta-strands. DSSP
>     tells me that,
>      > geometrically, I have beta-strands, but the visualization
>     software renders
>      > coil structures.
>      >
>      > In any case, large structural deviations during EM suggest something
>      > fundamentally wrong with the model. Usually the changes in EM are
>     small,
>      > since it is performed at 0 K. Only huge forces would cause any
>     sort of
>      > structural change.
>      >
>      >> I also want to ask what is the meaning of fx fy and fz :
>      >>
>      >
>      > Force constants (kJ mol^-1 nm^-2) in the x, y, and z directions.
>      >
>      >> ; atom type fx fy fz
>      >> 1 1 1000 1000 1000
>      >> 5 1 1000 1000 1000
>      >> 6 1 1000 1000 1000
>      >> 7 1 1000 1000 1000
>      >> 8 1 1000 1000 1000
>      >> 9 1 1000 1000 1000
>      >> 11 1 1000 1000 1000
>      >> 12 1 1000 1000 1000
>      >> 15 1 1000 1000 1000
>      >> 18 1 1000 1000 1000
>      >> 19 1 1000 1000 1000
>      >> 20 1 1000 1000 1000
>      >> 21 1 1000 1000 1000
>      >> 22 1 1000 1000 1000
>      >> 23 1 1000 1000 1000
>      >>
>      >> which is there in posre.itp file, and if these should have value
>     of 1000
>      >> 1000 1000 each ?
>      >>
>      >
>      > These default values are typically quite sufficient to restrain the
>      > structure.
>      >
>      > -Justin
>      >
>      >> Thanks in advance.
>      >> --
>      >> Sonali Dhindwal
>      >>
>      >>
>      >> --- On *Wed, 19/5/10, Gaurav Goel /<gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>>/* wrote:
>      >>
>      >>
>      >> From: Gaurav Goel <gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>>
>      >> Subject: Re: [gmx-users] enegry minimisation
>      >> To: "sonali dhindwal" <sonali11dhindwal at yahoo.co.in
>     </mc/compose?to=sonali11dhindwal at yahoo.co.in>>
>      >> Date: Wednesday, 19 May, 2010, 8:39 PM
>      >>
>      >> For position restraints you need to do the following:
>      >>
>      >> 1. define a name.itp file which looks like:
>      >>
>      >> ; In this topology include file, you will find position restraint
>      >> ; entries for all the heavy atoms in your original pdb file.
>      >> ; This means that all the protons which were added by pdb2gmx are
>      >> ; not restrained.
>      >>
>      >> [ position_restraints ]
>      >> ; atom type fx fy fz
>      >> 1 1 1000 1000 1000
>      >> 5 1 1000 1000 1000
>      >> 6 1 1000 1000 1000
>      >> .......
>      >> .......
>      >> _____
>      >> 1,5,6 etc. are the atom indices you want to restrain. section 4.3.1
>      >> in manual.
>      >>
>      >> 2. Add "define = -Dname" to your mdp file
>      >>
>      >> 3. Add following lines to your topology file
>      >> ; Include Position restraint file
>      >> #ifdef name
>      >> #include "name.itp"
>      >> #endif
>      >>
>      >> 4. compile and run.
>      >>
>      >> I'm sure you will find mroe information on position-restrain
>      >> simulation on gmx-users archive.
>      >>
>      >> -Gaurav
>      >>
>      >> On Wed, May 19, 2010 at 10:26 AM, sonali dhindwal
>      >> <sonali11dhindwal at yahoo.co.in
>     </mc/compose?to=sonali11dhindwal at yahoo.co.in>
>      >> </mc/compose?to=sonali11dhindwal at yahoo.co.in
>     </mc/compose?to=sonali11dhindwal at yahoo.co.in>>> wrote:
>      >>
>      >> Hello Gaurav,
>      >> Can you please help me in suggesting where should I look for
>      >> providing parameters to constrain the protein backbone and then
>      >> do EM and then how to run a short MD simulation by constraining
>      >> the protein backbone.
>      >> Sorry to bother you, but as I am new to Gromacs, your help will
>      >> be highly appreciable.
>      >> Thanks in advance
>      >>
>      >> --
>      >> Sonali Dhindwal
>      >>
>      >>
>      >> --- On *Wed, 19/5/10, Gaurav Goel /<gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>
>      >> </mc/compose?to=gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>>>/* wrote:
>      >>
>      >>
>      >> From: Gaurav Goel <gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>
>      >> </mc/compose?to=gauravgoeluta at gmail.com
>     </mc/compose?to=gauravgoeluta at gmail.com>>>
>      >>
>      >> Subject: Re: [gmx-users] enegry minimisation
>      >> To: "Discussion list for GROMACS users"
>      >> <gmx-users at gromacs.org </mc/compose?to=gmx-users at gromacs.org>
>     </mc/compose?to=gmx-users at gromacs.org
>     </mc/compose?to=gmx-users at gromacs.org>>>
>      >> Date: Wednesday, 19 May, 2010, 6:44 PM
>      >>
>      >>
>      >> After adding water you can do energy minimization (EM) in
>      >> two steps:
>      >>
>      >> 1. Constrain the protein backbone and do EM.
>      >> 2. Now do EM on the full system.
>      >> 3. Run a short MD simulation by constraining the protein
>      >> backbone.
>      >> The above three steps will help hydrate the protein molecule
>      >> with minimal distortion of protein structure.
>      >>
>      >> 4. Now run a MD on full system.
>      >>
>      >> for details looks here:
>      >>
>      >>
>     http://www.google.com/url?sa=t&source=web&ct=res&cd=2&ved=0CBcQFjAB&url=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdf&ei=jOPzS8a3Lab2MdX1_aAO&usg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymg&sig2=bY3NqXHmruR7eSLVyAuCHQ
>     <http://www.google.com/url?sa=t&source=web&ct=res&cd=2&ved=0CBcQFjAB&url=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdf&ei=jOPzS8a3Lab2MdX1_aAO&usg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymg&sig2=bY3NqXHmruR7eSLVyAuCHQ>
>      >>
>      >>
>     <http://www.google.com/url?sa=t&source=web&ct=res&cd=2&ved=0CBcQFjAB&url=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdf&ei=jOPzS8a3Lab2MdX1_aAO&usg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymg&sig2=bY3NqXHmruR7eSLVyAuCHQ
>     <http://www.google.com/url?sa=t&source=web&ct=res&cd=2&ved=0CBcQFjAB&url=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdf&ei=jOPzS8a3Lab2MdX1_aAO&usg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymg&sig2=bY3NqXHmruR7eSLVyAuCHQ>>
>      >>
>      >> -Gaurav
>      >>
>      >> On Wed, May 19, 2010 at 8:18 AM, sonali dhindwal
>      >> <sonali11dhindwal at yahoo.co.in
>     </mc/compose?to=sonali11dhindwal at yahoo.co.in>
>      >> <http://mc/compose?to=sonali11dhindwal@yahoo.co.in>> wrote:
>      >>
>      >> Sorry, but I couldnt get your question,
>      >> I have used this .mdp file for energy minimisation after
>      >> addition of water and using
>      >>
>      >> GROMOS96 43a1 force field :
>      >>
>      >>
>      >> title = drg_trp
>      >> cpp = /lib/cpp ; location of cpp on SGI
>      >> define = -DFLEX_SPC ; Use Ferguson’s Flexible water
>      >> model [4]
>      >> constraints = none
>      >> integrator = steep
>      >> dt = 0.002 ; ps !
>      >> nsteps = 2000
>      >> nstlist = 10
>      >> ns_type = grid
>      >> rlist = 0.9
>      >> coulombtype = PME ; Use particle-mesh ewald
>      >> rcoulomb = 0.9
>      >> rvdw = 1.0
>      >> fourierspacing = 0.12
>      >> fourier_nx = 0
>      >> fourier_ny = 0
>      >> fourier_nz = 0
>      >> pme_order = 4
>      >> ewald_rtol = 1e-5
>      >> optimize_fft = yes
>      >> ;
>      >> ; Energy minimizing stuff
>      >> ;
>      >> emtol = 1000.0
>      >> emstep = 0.01
>      >>
>      >> I hope it will help you to guide me further
>      >> Thanks
>      >> --
>      >> Sonali Dhindwal
>      >>
>      >>
>      >> --- On *Wed, 19/5/10, Erik Marklund
>      >> /<erikm at xray.bmc.uu.se </mc/compose?to=erikm at xray.bmc.uu.se>
>      >> <http://mc/compose?to=erikm@xray.bmc.uu.se>>/* wrote:
>      >>
>      >>
>      >> From: Erik Marklund <erikm at xray.bmc.uu.se
>     </mc/compose?to=erikm at xray.bmc.uu.se>
>      >> <http://mc/compose?to=erikm@xray.bmc.uu.se>>
>      >> Subject: Re: [gmx-users] enegry minimisation
>      >> To: "Discussion list for GROMACS users"
>      >> <gmx-users at gromacs.org </mc/compose?to=gmx-users at gromacs.org>
>      >> <http://mc/compose?to=gmx-users@gromacs.org>>
>      >> Date: Wednesday, 19 May, 2010, 5:31 PM
>      >>
>      >>
>      >> sonali dhindwal skrev:
>      >> > 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.
>      >> > I have noticed that after enegry minimisation
>      >> using steepest decent algorithm, using emtol of 1000
>      >> kJ mol^-1 nm^-1 , large amount of distortion occurs.
>      >> > 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.
>      >> > Thanks and regards
>      >> > ^
>      >> >
>      >> >
>      >> > --
>      >> > Sonali Dhindwal
>      >> >
>      >> >
>      >> So how has your system setup changed since your
>      >> previous EM? Addition of water? Cutoffs? PME?
>      >>
>      >> -- -----------------------------------------------
>      >> Erik Marklund, PhD student
>      >> Dept. of Cell and Molecular Biology, Uppsala
>      >> University.
>      >> Husargatan 3, Box 596, 75124 Uppsala, Sweden
>      >> phone: +46 18 471 4537 fax: +46 18 511 755
>      >> erikm at xray.bmc.uu.se </mc/compose?to=erikm at xray.bmc.uu.se>
>      >> <http://mc/compose?to=erikm@xray.bmc.uu.se>
>      >> http://folding.bmc.uu.se/
>      >>
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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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