[gmx-users] PMF curve in umbrella sampling

[Justin Lemkul]

On 8/29/14, 2:08 PM, Mana Ib wrote:
> Dear Users,
>
> I am doing an umbrella sampling for a protein-ligand complex, wherein I
> first did an SMD run for 500 ps and generated 500 configurations, the COM
> distances for these configurations start at 1.25nm for conf0 and so on till
> 6.4nm for conf500. Hence I used a 0.05nm spacing to select configurations
> for the umbrella sampling windows.
> I have currently completed running 2 windows, each window was subjected to
> a 5ns  mdrun.
>
> This is my mdp file parameters
>
> title       = Umbrella pulling simulation
> define      = -DPOSRES
> ; Run parameters
> integrator  = md
> dt          = 0.002
> tinit       = 0
> nsteps      = 2500000   ; 5 ns
> nstcomm     = 10
> ; Output parameters
> nstxout     = 50000     ; every 100 ps
> nstvout     = 50000
> nstfout     = 5000
> nstxtcout   = 5000      ; every 10 ps
> nstenergy   = 5000
> ; Bond parameters
> constraint_algorithm    = lincs
> constraints             = all-bonds
> continuation            = yes
> ; Single-range cutoff scheme
> nstlist     = 5
> ns_type     = grid
> rlist       = 1.4
> rcoulomb    = 1.4
> rvdw        = 1.4
> ; PME electrostatics parameters
> coulombtype     = PME
> fourierspacing  = 0.12
> fourier_nx      = 0
> fourier_ny      = 0
> fourier_nz      = 0
> pme_order       = 4
> ewald_rtol      = 1e-5
> optimize_fft    = yes
> ; Berendsen temperature coupling is on in two groups
> Tcoupl      = Nose-Hoover
> tc_grps     = Protein   Non-Protein
> tau_t       = 0.5       0.5
> ref_t       = 310       310
> ; Pressure coupling is on
> Pcoupl          = Parrinello-Rahman
> pcoupltype      = isotropic
> tau_p           = 1.0
> compressibility = 4.5e-5
> ref_p           = 1.0
> refcoord_scaling = com
> ; Generate velocities is off
> gen_vel     = no
> ; Periodic boundary conditions are on in all directions
> pbc     = xyz
> ; Long-range dispersion correction
> DispCorr    = EnerPres
> ; Pull code
> pull            = umbrella
> pull_geometry   = distance
> pull_dim        = Y N N
> pull_start      = yes
> pull_ngroups    = 1
> pull_group0     = Chain_A
> pull_group1     = NL
> pull_init1      = 0
> pull_rate1      = 0.0
> pull_k1         = 500      ; kJ mol^-1 nm^-2
> pull_nstxout    = 1000      ; every 2 ps
> pull_nstfout    = 1000      ; every 2 ps
>
>
> When I use g_wham to plot the histogram and PMF curve for these 2 windows,
> my plots don't seem to follow the general trend as given in
> tutorials..(figure links below). Is this discrepancy because I have used
> only files from 2 windows to plot these? Or are these due to some other
> errors in the protocol?
>
> http://i46.photobucket.com/albums/f121/fullmeasure29/histo_2win_zpsff19fe60.png
>
> http://i46.photobucket.com/albums/f121/fullmeasure29/pmf_2win_zps04adb8f7.png
>

The two windows yield effectively overlapping distributions and a meaningless 
PMF.  Space the windows further (0.05 nm is very tight) and run more windows for 
a real PMF as a function of a meaningful reaction coordinate.

-Justin

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

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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