[gmx-users] Energy minimisation goes to several values

[Justin Lemkul]

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>>
>> <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>>
>> *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>>
>> *Reply-To:*<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>|
>> (410) 706-7441
>> 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 | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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