[gmx-users] Umbrella Sampling Results and Issues

[HANNIBAL LECTER]

Another simulation between the third and the fourth replica and you should
be fine. I don't think what you are observing is an artifact of
insufficient sampling time.

On Mon, Nov 24, 2014 at 1:03 PM, Agnivo Gosai <agnivogromacs14 at gmail.com>
wrote:

> Dear Users
>
> I am doing an umbrella sampling MD to calculate the binding energy between
> a DNA and a protein. I am following Dr. Lemkuls tutorial for the same.
>
> Firstly I put the complex in a rectangular box and used the
> AMBER99SB-Parmbsc0 forcefield for the topology generation. Then I used SD
> for minimization , 1 ns restrained NVT equilibration ( V-rescale , T = 300
> K) , 1 ns restrained NPT equilibration ( Berendsen couplings in both , ref
> Press = 1 bar , however achieved average press = 0.4 bar with very low
> error , RMSD ) , 500 ps Steered Molecular Dynamics keeping DNA fixed and
> pulling Protein ( Using Nose-Hoover thermostat , Parinello - Rahman
> barostat ).
>
> I pull for a total of 5 nm.
>
> This is the relevant mdp entry for the SMD
>
> ; Pull code
> pull            = umbrella
> pull_geometry   = distance  ; simple distance increase
> pull_dim        = N N Y     ; Z axis reaction coordinate
> pull_start      = yes       ; define initial COM distance > 0
> pull_ngroups    = 1         ; applying puling force to protein only
> pull_group0     = DNA       ; reference fixed group for pulling
> pull_group1     = Protein   ; the molecule to which pulling force is
> applied
> pull_rate1      = 0.01      ; 0.01 nm per ps = 10 nm per ns
> pull_k1         = 1000      ; kJ mol^-1 nm^-2 force constant for pulling
>
> After this I extracted the conf.gro files and using the perl/python scripts
> from the tutorial extracted 21 windows (0.2 nm spacing) from the SMD
> trajectory for the umbrella sampling. In each window I did a 100 ps short
> NPT equilibration restraining only the DNA and then an 1 ns umbrella
> sampling simulation restraining the DNA with the following mdp entry :
>
> ; Pull code
> pull            = umbrella
> pull_geometry   = distance
> pull_dim        = N N Y
> pull_start      = yes
> pull_ngroups    = 1
> pull_group0     = DNA
> pull_group1     = Protein
> pull_init1      = 0
> pull_rate1      = 0.0
> pull_k1         = 1000      ; kJ mol^-1 nm^-2
> pull_nstxout    = 100      ; every 0.2 ps
> pull_nstfout    = 100      ; every 0.2 ps
>
> Then I ran the g_wham tool on the results.
>
> I am attaching the PMF profile and the Histogram for reference :
>
> ​
>  PMF
> <
> https://docs.google.com/file/d/0B-U8uULVZjfRaHE4STc2QVo3VmM/edit?usp=drive_web
> >
> ​​
>  HISTOGRAM
> <
> https://docs.google.com/file/d/0B-U8uULVZjfRZ2IxbXZSeTc1QUE/edit?usp=drive_web
> >
> ​
> As observed , the PMF is having 3 steps for particular reaction coordinates
> and at those regions the Histogram is also not showing ideal overlapping
> behaviour.
>
> This is the ERROR output of g_wham :
>
> WARNING, no data point in bin 26 (z=3.04567) !
> You may not get a reasonable profile. Check your histograms!
>
> The error file is also attached :
>
> ​
>  WHAM1_ERROR.txt
> <
> https://docs.google.com/file/d/0B-U8uULVZjfRbkllV1hZLXR6MjQ/edit?usp=drive_web
> >
> ​
> So, my questions are :
>
> Should I decrease the nm spacing to say 0.1 nm around those particular
> reaction coordinates where the "no data point in bin" error is coming ? ?
> Should I be going for asymmetric windows
>
> OR , should I simultaneously increase my simulation time for umbrella
> sampling to say 5 ns from 1 ns ?
>
> Kindly suggest
>
> ------------------------------------------------------------------------
>
>
> Thanks & Regards
> Agnivo Gosai
> Grad Student, Iowa State University.
> --
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