[gmx-users] EM curve question

[Justin A. Lemkul]

parto haghighi wrote:
> Dear Mark,
> Thanks for your answer.
> I have done these steps:
> 1. Prepare ligand topology by PRODRG server (like fifth gromacs tutorial)

Did you adequately correct the parameters therein?  As noted in that tutorial 
(and elsewhere), the charges and charge groups produced by PRODRG are not reliable.

> 2. Download lipid.itp file and make new force field for it (like second 
> gromacs tutorial)
> 3. Use editconf and cat to prepare a system with 12 ligand in both sides 
> of lipid.

So the small molecules you've added are embedded in the membrane?  How did you 
insert them?  If not done carefully, you'll have extreme atomic overlap here.

> 4. Add wares
> 5 . Add 8 CL
> 
> [ molecules ]
> ; Compound        #mols
> DRG             12
> DMPC            128
> SOL         1976

With such little water, this membrane is not adequately solvated, unless you're 
looking to model a dehydrated state.

> CL          12
> 
> 5. Use these parameters in minim.mdp file:
> 
> Integrator    = steep
> emtol         = 1000.0
> emstep      = 0.0001
> nsteps       = 50000
> nstlist         = 1     
> ns_type      = grid   
> rlist             = 1    
> coulombtype    = PME 
> rcoulomb     = 1   
> rvdw           = 1     
> pbc            = xyz    
> 
> Statistics over 397 steps [ 1.0000 through 397.0000 ps ], 1 data sets
> All statistics are over 319 points (frames)
> 
> Energy                      Average   Err.Est.       RMSD  Tot-Drift
> -------------------------------------------------------------------------------
> Potential                6.00519e+09    5.5e+09 2.98259e+10 
> -3.30965e+10  (kJ/mol)
> 
> Its value is positive and after:
> g_energy -f em.edr its curve converges to zero.
> Help me to correct its parameter if its possible.

See suggestions above.  I suspect poor parameters, incorrect system preparation, 
or both, are to blame here.

> I have another question, should I do energy minimization after adding 
> each ligand molecules to bilayer?
> 

That depends on how they have been added.  Careful insertion that is accompanied 
by lipid deletion or inflation (methodology akin to InflateGRO) should not 
require independent EM after each addition.

-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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