[gmx-users] Energy minimisation goes to several values

[Mark Abraham]

Hi,

I think one should only care so much about one's initial structure if the
purpose of the MD simulation is to observe whether it is preserved.
(Whether that's a worthwhile thing is a separate question.) And then only
if a simple equilibration protocol produces a measurable deviation that
seems attributable to the protocol rather than defects in the assumption
that (e.g.) a crystal structure corresponds to a solvated phase.

For other kinds of work, I do consider multi-phase equilibration protocols
only when there are issues to manage (e.g. change of density, equil of
velocities before using some kinds of v-sites)

Mark

On Mon, Jun 29, 2015 at 9:32 AM Kevin C Chan <cchan2242-c at my.cityu.edu.hk>
wrote:

> Thanks Justin again for the reply.
>
> Your example was very clear and I would rather drop such minimization
> protocol. Honestly such protocol comes from the conventional step-wise
> relaxation (or pre-equilibrium) practice for protein MD simulations. I
> believe you must have heard people constraining heavy atoms (carbon alpha
> atoms or sometimes even the backbone) during heating, box relaxation and
> then releasing them by decreasing the spring constant step-by-step before
> they started a production on the protein. So how do you comment on this
> stepwise protocol? If it is applicable, should it be turned on during
> energy minimization or just started from heating?
>
> Thanks in advance,
> Kevin
>
>
> > On 27 Jun, 2015, at 07:54, <
> gromacs.org_gmx-users-request at maillist.sys.kth.se> <
> gromacs.org_gmx-users-request at maillist.sys.kth.se> wrote:
> >
> > From: Justin Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
> > Subject: Re: [gmx-users] Energy minimisation goes to several values
> > Date: 27 June, 2015 07:54:13 HKT
> > To: Discussion list for GROMACS users <gmx-users at gromacs.org <mailto:
> gmx-users at gromacs.org>>
> > Reply-To: <gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>>
> >
> >
> >
> >
> > On 6/26/15 11:54 AM, Kevin C Chan wrote:
> >> Thanks Justin for the reply.
> >>
> >> Honestly I thought minimizing a large and complex (usually
> biomolecular) system
> >> part by part instead of as a whole will effectively shorten the
> computational
> >> time cost while causing no effect on the final structure. When you say
> >> “impedes”, do you mean it causes a longer calculation time in total or
> it will
> >> give a bad final structure?
> >>
> >
> > Well, you're running three minimizations instead of one, and you're
> achieving an unstable result.  I'd say the three-step approach is not worth
> doing :)
> >
> > Consider something really simple - a polar, surface residue on a protein
> surrounded by water.  Let's say you freeze the protein and let the water
> relax.  The local waters respond to the fixed geometry of the side chain,
> which is (maybe) from a crystal and therefore perhaps not the correct
> conformation in solution.  So the waters reorganize a bit.  Then you let
> the protein relax but the waters are fixed.  The side chain responds to a
> fixed clathrate of water that have been minimized around the wrong side
> chain conformation.  What have you achieved?  Nothing.  Sure, you then
> minimize the whole system, but your starting point is potentially less
> plausible than it was to start with!  At minimum, it's just a waste of
> time.  Occasional use of restraints can be beneficial in some cases.  Any
> time you talk about absolutely fixing large groups of atoms (like
> immobilizing water), I think it's really a waste of time.
> >
> > If a single, unrestrained minimization still leads to an unstable
> system, then it's not your minimization protocol that's to blame, rather an
> unresolvable starting structure or a bad topology.
> >
> > -Justin
> >
> >> Thanks in advance,
> >> Kevin
> >>
> >>> On 26 Jun, 2015, at 22:21, <
> gromacs.org_gmx-users-request at maillist.sys.kth.se <mailto:
> gromacs.org_gmx-users-request at maillist.sys.kth.se>
> >>> <mailto:gromacs.org_gmx-users-request at maillist.sys.kth.se <mailto:
> gromacs.org_gmx-users-request at maillist.sys.kth.se>>>
> >>> <gromacs.org_gmx-users-request at maillist.sys.kth.se <mailto:
> gromacs.org_gmx-users-request at maillist.sys.kth.se>
> >>> <mailto:gromacs.org_gmx-users-request at maillist.sys.kth.se <mailto:
> gromacs.org_gmx-users-request at maillist.sys.kth.se>>> wrote:
> >>>
> >>> *From:*Justin Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
> <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>>
> >>> *Subject:**Re: [gmx-users] Energy minimisation goes to several values*
> >>> *Date:*26 June, 2015 21:27:32 HKT
> >>> *To:*<gmx-users at gromacs.org <mailto:gmx-users at gromacs.org> <mailto:
> gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>>>
> >>> *Reply-To:*<gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>
> <mailto:gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>>>
> >>>
> >>>
> >>>
> >>>
> >>> On 6/25/15 9:45 PM, Kevin C Chan wrote:
> >>>> Dear Users,
> >>>>
> >>>> I am energy minimising a quite large solvated system containing
> protein and
> >>>> lipids (~800,000 atoms). I used to fix components of the system in
> order to
> >>>> speed-up energy minimisation and sometimes it is easier to debug such
> >>>> processes. Here is my protocol:
> >>>> 1. fix all except water and so to minimise water
> >>>> 2. fix water and then minimise all the rest atoms
> >>>> 3. fix nothin and then minimise the whole system
> >>>>
> >>>> While monitoring the energy of the system thought minimisations, it
> goes
> >>>> fine for step 1 and 2 and converged after just few hundred steps.
> However
> >>>> it goes back to several higher values of energy (bouncing between the
> >>>> values) and they started to increase very slowly for step 3. This
> makes no
> >>>> sense to me and did anyone have a similar experience?
> >>>>
> >>>> There are two unusual points:
> >>>> 1. The system energy drops suddenly instead of decreased gradually
> during
> >>>> step2 and then stays at a constant value.
> >>>> 2. If I use the resulting structure from step3 to proceed a, say,
> heating
> >>>> process, it simply blows up.
> >>>>
> >>>> To be clear, my system was solvated and auto-ionized using VMD tools
> and
> >>>> some water inside the membrane has been directly deleted. Backbone of
> the
> >>>> protein and phosphorus atoms of the membrane are under a
> >>>> position constraint during all the minimisations. I was choosing
> conjugate
> >>>> gradient for minimization.
> >>>>
> >>>
> >>> Does a "normal" minimization (just one overall minimization with
> nothing
> >>> fixed) yield a stable starting point?  Fixing atoms (using
> freezegrps?) often
> >>> actually impedes minimization.
> >>>
> >>> -Justin
> >>>
> >>> --
> >>> ==================================================
> >>>
> >>> Justin A. Lemkul, Ph.D.
> >>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >>>
> >>> Department of Pharmaceutical Sciences
> >>> School of Pharmacy
> >>> Health Sciences Facility II, Room 629
> >>> University of Maryland, Baltimore
> >>> 20 Penn St.
> >>> Baltimore, MD 21201
> >>>
> >>> jalemkul at outerbanks.umaryland.edu <mailto:
> jalemkul at outerbanks.umaryland.edu> <mailto:
> jalemkul at outerbanks.umaryland.edu <mailto:
> jalemkul at outerbanks.umaryland.edu>>|
> >>> (410) 706-7441
> >>> http://mackerell.umaryland.edu/~jalemkul <
> http://mackerell.umaryland.edu/~jalemkul>
> >>>
> >>> ==================================================
> >>
> >
> > --
> > ==================================================
> >
> > Justin A. Lemkul, Ph.D.
> > Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >
> > Department of Pharmaceutical Sciences
> > School of Pharmacy
> > Health Sciences Facility II, Room 629
> > University of Maryland, Baltimore
> > 20 Penn St.
> > Baltimore, MD 21201
> >
> > jalemkul at outerbanks.umaryland.edu <mailto:
> jalemkul at outerbanks.umaryland.edu> | (410) 706-7441
> > http://mackerell.umaryland.edu/~jalemkul <
> http://mackerell.umaryland.edu/~jalemkul>
> >
> > ==================================================
>
> --
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