[gmx-users] Simulation explodes (protein-ligand-protein)

[Justin A. Lemkul]

Giovana Bergamini wrote:
> 
>> Hi!
>> We have a problem with a protein-ligand-protein simulation. It is a somewhat
>> large system (approx. 360 amino acid residues with approx. 70 monosaccharides),
>> that requires a larger box for proper simulation.
>> We used exclusions (especifically for the problematic atoms) and restrictions
>> (tested values of 5000, 2000, 1000 - for backbone and for monosaccharides),
>> both combined and individually, and when they were kept for the entire
>> simulation, it went just fine. But when these restrictions and exclusions were
>> removed, the glycan portion, that isn’t connected to any of the proteins
>> “explodes”.
>> Any suggestions?
>>
>> Thank you in advance,
> 
> Hi,
> 
> We used the gromos43a1 force fied, and the .mdp with minimization parameters
> with no restraints or exclusions were:
> 
> title               =  Yo
> cpp                 =  /lib/cpp
> define		    =  -DFLEX
> constraints         =  all-bonds
> integrator          =  md
> tinit               =  0000
> dt                  =  0.0005	; ps !
> nsteps              =  2000000	; total 00000-1000 ps.
> nstcomm             =  1
> nstxout             =  250
> nstvout             =  1000
> nstfout             =  0
> nstlog              =  100
> nstenergy           =  100
> nstlist             =  10
> ns_type             =  grid
> coulombtype         =  PME
> rlist               =  0.9
> rcoulomb            =  0.9
> rvdw                =  0.9
> fourierspacing      =  0.12
> optimize_fft	    =  yes
> pme_order           =  4
> ewald_rtol          =  1e-5
> ; Berendsen temperature coupling is on in four groups
> Tcoupl              =  berendsen
> tc-grps		    =  Protein_1 Protein_2 gli_1 gli_2 gli_3 gli_4 gli_5 CA+
> tau_t               =  0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
> ref_t               =  50 50 50 50 50 50 50 50
> ; Energy monitoring
> energygrps          =  Protein_1 Protein_2 gli_1 gli_2 gli_3 gli_4 gli_5 CA+
> ; Isotropic pressure coupling is now on
> Pcoupl              =  berendsen
> Pcoupltype          =  isotropic
> tau_p               =  0.5
> compressibility     =  4.5e-5
> ref_p               =  1.0
> ; Generate velocites is off at 100 K.
> gen_vel             =  yes
> gen_temp            =  10.0
> gen_seed            =  173529
> 
> This .mdp file works fine without water, but when we include "sol" the
> simulation explodes, too.
> The tc-grps in this case are a glycoprotein (protein-1, gli_1, gli_2, gli_3,
> gli_4 and gli_5) and a secondary protein (protein-2).
> 

Are each of these groups sufficiently large to justify their own temperature 
coupling group?  I'd be especially concerned about coupling ions alone 
(presumably there are only a few CA+?)

http://www.gromacs.org/Documentation/Terminology/Thermostats

If you can identify that certain molecules are unstable, then I'd suspect as 
well that there might be problems with the topology.  How did you generate it? 
How did you validate the parameters?  Do simulations of the sugar moieties alone 
(using your topology) run stably?

-Justin

> thank you again,
> 
> 
> Giovana Bergamini
> Faculdade de Farmácia
> Grupo de Bioinformatica Estrutural
> Universidade Federal do Rio Grande do Sul
> Av. Bento Gonçalves, 9500
> Prédio 43431, sala 202
> CEP 91500-970, CP 15005, Porto Alegre, RS, Brazil
> tel.: +55 51 3308 7770
> http://www.cbiot. ufrgs.br/ bioinfo
> 
> 
> --------------------------------------------------------------------
> Centro de Biotecnologia da Universidade Federal do Rio Grande do Sul

-- 
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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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