[gmx-users] protein getting unfolded in SPC/E water

[Justin Lemkul]

On 9/15/16 11:46 AM, soumadwip ghosh wrote:
> Hello,
>          I am simulating Lysozyme in pure SPC/E water for 200 ns. I am
> using OPLS-AA force field for my work. In pure water the protein looses
> some of its helices. As for example in the final md.gro file the number of
> alpha helices observed are 2 while in the beginning 4 were observed in VMD.

Loading two coordinate files in VMD and comparing them is not a rigorous 
assessment.  Most visualization programs are pretty notorious for simply 
rendering secondary structure wrong.  What does a real analysis, like DSSP or a 
dihedral time series, tell you?

> The corresponding C-alpha RMSD and radius of gyration are also fluctuating.
> Could anyone help me understand what's going on?

RMSD and Rg will always fluctuate.  A large, systematic drift would be a 
problem.  Fluctuation is not.

-Justin

> I am pasting the snippets of my topology and the md.mdp files.
>
>
> ; Include water topology
> #include "oplsaa.ff/spce.itp"
>
> #ifdef POSRES_WATER
> ; Position restraint for each water oxygen
> [ position_restraints ]
> ;  i funct       fcx        fcy        fcz
>    1    1       1000       1000       1000
> #endif
>
> ; Include topology for ions
> #include "oplsaa.ff/ions.itp"
>
> [ system ]
> ; Name
> Protein in water
>
> [ molecules ]
> ; Compound        #mols
> Protein_chain_A     1
> SOL         11071
> CL               9
> Here is the md.mdp one
>
> constraints     = all-bonds     ; all bonds (even heavy atom-H bonds)
> constrained
> lincs_iter      = 1             ; accuracy of LINCS
> lincs_order     = 4             ; also related to accuracy
> ; Neighborsearching
> ns_type         = grid          ; search neighboring grid cells
> nstlist         = 5             ; 10 fs
> rlist           = 1.0           ; short-range neighborlist cutoff (in nm)
> rcoulomb        = 1.0           ; short-range electrostatic cutoff (in nm)
> rvdw            = 1.0           ; short-range van der Waals cutoff (in nm)
> ; Electrostatics
> coulombtype     = PME           ; Particle Mesh Ewald for long-range
> electrostatics
> pme_order       = 4             ; cubic interpolation
> fourierspacing  = 0.16          ; grid spacing for FFT
> ; Temperature coupling is on
> tcoupl          = V-rescale     ; modified Berendsen thermostat
> tc-grps         = SYSTEM        ; two coupling groups - more accurate
> tau_t           = 0.1           ; time constant, in ps
> ref_t           = 310           ; reference temperature, one for each
> group, in K
> ; Pressure coupling is on
> pcoupl          = Parrinello-Rahman     ; Pressure coupling on in NPT
> pcoupltype      = isotropic     ; uniform scaling of box vectors
> tau_p           = 2.0           ; time constant, in ps
> ref_p           = 1.0           ; reference pressure, in bar
> compressibility = 4.5e-5        ; isothermal compressibility of water,
> bar^-1
> ; Periodic boundary conditions
> pbc             = xyz           ; 3-D PBC
> ; Dispersion correction
> DispCorr        = EnerPres      ; account for cut-off vdW scheme
> ; Velocity generation
> gen_vel         = no            ; Velocity generation is off
> energygrps      = protein SOL
>
> I am quite sure that the system is well equilibrated.
>
> Here is the part of md.edr file
>
> Back Off! I just backed up energy.xvg to ./#energy.xvg.2#
> Last energy frame read 75000 time 150000.000
>
> Statistics over 75000001 steps [ 0.0000 through 150000.0000 ps ], 4 data
> sets
> All statistics are over 15000001 points
>
> Energy                      Average   Err.Est.       RMSD  Tot-Drift
> -------------------------------------------------------------------------------
> Temperature                 310.004     0.0015    1.64028 0.000388793  (K)
> Pressure                    1.04308    0.00049    143.118 0.00201836  (bar)
> Volume                      351.008     0.0063   0.835859  0.0314951  (nm^3)
> Density                     1012.78      0.018    2.41171 -0.0908186
>  (kg/m^3)
>
>
> What might go wrong?
> Thanks for your time in advance.
>
> Soumadwip Ghosh
> Senior Research Fellow
> Indian Institute of Technology Bombay
> India
>

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

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

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