[gmx-users] Peptide - DMPC membrane simulations -> Unstable system

[Justin A. Lemkul]

Kirill Bessonov wrote:
> I think I have not arrived to complete solution of my problem yet, but I 
> think the cause of early LINCS warnings were version incompatibility. I 
> am now trying to run simulation on the server that has only 4.0.5 
> Gromacs, will see if that helps and whether I will warnings in the 
> middle of simulations.
> 
> I have tried PR simulation on peptide and it failed even earlier (after 
> 10,000 steps), maybe this indicates version issues, as I would assume PR 
> simulations are more stable as they does not allow peptide to enter DMPC 
> layer ....
> 

Right; rule out the version as a problem first.

> So after 20 ns of simulation on the server with Gromacs 4.0 I've started 
> to get errors and LINCS warnings and simulation collapsed, I have 
> resumed simualtion as per oldwiki instructions, but again it soon 
> failed. After looking at the trajectory with VMD I see that the peptide 
> "sinks" into DMPC and one phenyl ring flips out (Phe residue). Maybe due 
> to local constrains and being surrounded by DMPC the errors start coming 
> up. I am not sure.  I will do the movie and post it on youtube as ato 
> show you what is going on.
> 

So does this "sinking" behavior always correlate with a LINCS crash?  Or is the 
crashing sporadic?  I wouldn't base any conclusions based on 4.0 simulations - 
get results from 4.0.5 before diagnosing.

> Why does the system fails after 10,578,600 steps? Is there way to ignore 
> LINCS warnings and make simulation run anyways, if yes how?
> 

LINCS warnings cannot be ignored.  They indicate instability in the system, 
either because of a bug (one that I identified in version < 4.0.2), or because 
your method of running the simulation is incorrect (force field, .mdp 
parameters, system preparation, etc).  Note that I commented on your treatment 
of temperature and pressure coupling, as well as COM motion removal previously 
as being potentially problematic.

> I was not sure what to try next. Try to do several EM steps to get 
> system to 500 kJ/mol, right now it is at 800 kJ/mol?
> 

It may or may not be feasible to achieve an Fmax this low.  I think 800 is fine; 
many systems that run stably do not even get this low, in my own experience.

> Or try to do longer equilibration steps by restraining protein using 
> posre.itp file included in topology as per your tutorial?
> 

I really think proper equilibration is necessary (with restraints on the 
protein).  Never have I seen anyone report in the literature, "following energy 
minimization, unrestrained simulations were initiated and data collection 
begun."  I would seriously question that methodology (see my comments in 
previous messages).

-Justin

> Thanks for your time.
> 
> 
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-- 
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Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
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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