[gmx-users] UREA + Protein Simulation error.

[Justin A. Lemkul]

karan syal wrote:
> Dear Gromacs users,
> 
> I am trying to run a urea+protein simulation and encountering a few 
> problems at various stages.
> 
> I have taken an equilibrated 10M urea box of size 2.84nmx2.84nmx2.84nm 
> (I started with 3x3x3 containing 160 urea + 398 SOL, ran NPT @ 1 bar and 
> 300K)
> 
> I am using this equilibrated box to add to a globular protein of about 
> 250 residues using following commands :
> 
> 
> editconf -f P48.gro -o P48_box.gro -c -d 0.6 -bt dodecahedron    (Giving 
> me a dodecahedron with Vol = 407.98nm^3, so for this volume, for 10M 
> urea the number of urea above box should add is 2448.)
> 
> genbox -cp P48_box.gro -cs 10Murea.gro -o P48_10MUrea.gro   (*This adds 
> 2064 Urea only, shouldnt it be adding 2448 urea molecules, corresponding 
> to 10M urea box i have solvated with??)*
> 

No, it shouldn't.  The protein occupies space within that volume, as well.

> 
> When i try to minimize this using the following em.mdp
> 
> 
> cpp                 =  /usr/bin/cpp
> constraints         =  none
> integrator          =  steep
> nsteps              =  5000
> coulombtype = PME
> pme_order = 4
> nstlist = 5
> ns_type = grid
> rlist               =  1.0
> rcoulomb            =  1.0
> rvdw                =  1.0
> Tcoupl              =  no
> Pcoupl              =  no
> fourierspacing = 0.12
> fourier_nx = 0
> fourier_ny = 0
> fourier_nz = 0
> ;       Energy minimizing stuff
> ;
> emtol               =  100
> emstep              =  0.01
> 
> 
> *It gives me the following output*
> 
> 
> Steepest Descents:
>    Tolerance (Fmax)   =  1.00000e+02
>    Number of steps    =         5000
> Warning: 1-4 interaction between 2796 and 2801 at distance 2.727 which 
> is larger than the 1-4 table size 2.000 nm
> These are ignored for the rest of the simulation
> This usually means your system is exploding,
> if not, you should increase table-extension in your mdp file
> or with user tables increase the table size
> 
> t = 0.015 ps: Water molecule starting at atom 34477 can not be settled.
> Check for bad contacts and/or reduce the timestep.
> Wrote pdb files with previous and current coordinates
> 
> Stepsize too small, or no change in energy.
> Converged to machine precision,
> but not to the requested precision Fmax < 100
> 
> Double precision normally gives you higher accuracy.
> You might need to increase your constraint accuracy, or turn
> off constraints alltogether (set constraints = none in mdp file)
> 
> writing lowest energy coordinates.
> 
> Steepest Descents converged to machine precision in 34 steps,
> but did not reach the requested Fmax < 100.
> Potential Energy  = -1.3092671e+22
> Maximum force     =            inf on atom 12598
> Norm of force     =            inf
> 
> gcq#160: "The Microsecond is Within Reach" (P.J. Van Maaren)
> 
> 
> 
> /When i look at the file in VMD, the protein is completely out of the 
> box + There are unusual bonds between a lot of UREA and SOL molecules/. 
> ( The unusual bonds are artifcats after minimization which are not there 
> when i initially look at my P48_10Mrea.gro, that is the gro generated 
> after genbox wth -cs as 10M urea)
> 

"Out of the box" doesn't exist for a periodic system.  The "bonds" you see are 
also *not* generated by Gromacs, but are also just an artefact of visualization. 
  Bonds are not created or broken in molecular mechanics.

> I tried constraining hbonds as well in em.mdp bit to no effect.
> 
> 
> I used the above em.gro to run a production run, with following pr.mdp
> 

Don't, it's a waste of time.  Never just plow ahead when something isn't 
working.  There is something unreasonable about the starting structure.  Try 
minimizing the protein in vacuo first, then add your urea and try EM again.

-Justin

-- 
========================================

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

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