[gmx-users] Peptide folding simulation

[Justin A. Lemkul]

On 7/9/12 12:02 AM, bharat gupta wrote:
> Hi,
>
>
> I have been trying to study folding of a peptide 24 residues long. I
> did  a  simulation of 50 ns with explicit solvent, CHARMM FF, but I
> was not able to find even a single folding event. Then I decided use
> explicit solvent for simulation and I again simulated the peptide for
> 100 ns . This time again I ended with no folding events.
>
>
>   I know that in case of explicit solvent , a 50ns simulation time is
> not enough to observe anything. But I did it to see the initial
> behavior of the peptide in water. In take many random like
> conformation but doesnot fold into a desired beta-hairpin. For the
> explicit solvent simulation, I followed the lysozyme tutorial
> parameters.
>

You shouldn't.  The .mdp settings are appropriate for OPLS-AA, not CHARMM.

> For implicit solvent simulation, I used the following parameters for
> Energy minimization  :
>
>   define              =  -DFLEXIBLE
>   constraints         =  none
>   integrator          =  steep
>   dt                  =  0.001    ; ps
>   nsteps              =  30000
>   vdwtype             =  cut-off
>   coulombtype         =  cut-off
>   pbc                 =  no
>   nstlist             =  0
>   ns_type             =  simple
>   rlist               =  0       ; this means all-vs-all (no cut-off),
> which   gets expensive for bigger systems
>   rcoulomb            =  0
>   rvdw                =  0
>   comm-mode           =  angular
>   comm-grps           =  Protein
>   optimize_fft        =  yes
>   ;
>   ;       Energy minimizing stuff
>   ;
>   emtol               =  5.0
>   emstep              =  0.01
>   ;
>   ; Implicit solvent
>   ;
>   implicit_solvent    =  GBSA
>   gb_algorithm        =  Still ; HCT ; OBC
>   nstgbradii          =  1
>   rgbradii            =  0   ; [nm] Cut-off for the calculation of the
> Born  radii. Currently must be equal to rlist
>   gb_epsilon_solvent  =  80    ; Dielectric constant for the implicit  solvent
>    ; gb_saltconc       =  0     ; Salt concentration for implicit
> solvent  models, currently not used
>   sa_algorithm        =  Ace-approximation
>   sa_surface_tension  = -1
>
>
>
> For MD I used the following : -
>
>
> define              =  -DPOSRESHELIX ; -DFLEXIBLE -DPOSRES
>   constraints         =  none
>   integrator          =  md
>   dt                  =  0.001   ; ps
>   nsteps              =  1000000000 ; 100000 ps = 100 ns
>   nstcomm             =  10
>   nstcalcenergy       =  10
>   nstxout             =  1000     ; frequency to write coordinates to output
>   trajectory
>   nstvout             =  0       ; frequency to write velocities to output
>   trajectory; the last velocities are always written
>   nstfout             =  0       ; frequency to write forces to output
>   trajectory
>   nstlog              =  1000         ; frequency to write energies to log
>   file
>   nstenergy           =  1000     ; frequency to write energies to edr file
>
>   vdwtype             =  cut-off
>   coulombtype         =  cut-off
>
>   pbc                 =  no
>
>   nstlist             =  0
>   ns_type             =  simple
>   rlist               =  0       ; this means all-vs-all (no cut-off), which
>   gets expensive for bigger systems
>   rcoulomb            =  0
>   rvdw                =  0
>
>   comm-mode           =  angular
>   comm-grps           =  system
>
>   optimize_fft        =  yes
>
>   ; V-rescale temperature coupling is on
>   Tcoupl              =  v-rescale
>   tau_t               =  0.1
>   tc_grps             =  system
>   ref_t               =  300
>   ; Pressure coupling is off
>   Pcoupl              =  no
>   ; Generate velocites is on
>   gen_vel             =  yes
>   gen_temp            =  300
>   gen_seed            =  -1
>
>   ;
>   ; Implicit solvent
>   ;
>   implicit_solvent    =  GBSA
>   gb_algorithm        =  Still ; HCT ; OBC
>   nstgbradii          =  1
>   rgbradii            =  0   ; [nm] Cut-off for the calculation of the
> Born radii. Currently must be equal to rlist
>   gb_epsilon_solvent  =  80    ; Dielectric constant for the implicit   solvent
>   ; gb_saltconc       =  0     ; Salt concentration for implicit
> solvent   models, currently not used
>   sa_algorithm        =  Ace-approximation
>   sa_surface_tension  = -1
>
> So, finally I want to know where have I gone in my simulation
> experiments, both implicit and explicit ?? ... Please reply .
>

What evidence do you have that you should expect to see a folding event in such 
a short time?  Most people will use more extensive sampling methods like REMD to 
observe peptide folding.

-Justin

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

Justin A. Lemkul, Ph.D.
Research Scientist
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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