# [gmx-users] Problem in PCA of protein ligand system

Tsjerk Wassenaar tsjerkw at gmail.com
Mon Sep 26 12:37:54 CEST 2016

```Hi Ashutosh,

If you want to look at specific motions, like a dihedral, then just look at
that (gmx angle).

Cheers,

Tsjerk

On Mon, Sep 26, 2016 at 11:10 AM, ashutosh srivastava <ashu4487 at gmail.com>
wrote:

> Dear Tsjerk
>
> Thank you so much for the detailed explanation.
> So is there a way to extract motions of only ligand, along a particular
> direction (say rotation along a dihedral in ligand) from this trajectory?
>
> Best Regards
> Ashutosh
>
> On Mon, Sep 26, 2016 at 3:52 PM, Tsjerk Wassenaar <tsjerkw at gmail.com>
> wrote:
>
> > Hi Ashutosh,
> >
> > To simplify this, let's do PCA of two balls on opposite ends of a stick
> I'm
> > rotating. The mean position of both ends is right at the center of
> > rotation, and the relative positions I can describe with X and Y
> > coordinates only. Now, the essence of PCA is the question 'which single
> > direction can I find that explains most of the spread of my points?'.
> Since
> > this is pure rotation, any direction is as good as any other, so I just
> > pick the horizontal line through the center. I then project my trajectory
> > onto this axis. Surprise: I find that the principal component describes
> > lengthening and contraction of my stick along the horizontal direction.
> > What? Let's check the other component, orthogonal to the first. That too
> > describes lengthening and contraction, but anticorrelated with the
> > projection onto the first. The thing is, I can't ever describe a
> > ((semi-)rigid) rotation with a single component. The projection needs to
> go
> > through the center and come out the other end, looking like a contraction
> > and expansion. Likewise, the mean structure is halfway, so it's the most
> > distorted configuration along the axis.
> >
> > I hope this clarifies your observations.
> >
> > Cheers,
> >
> > Tsjerk
> >
> > On Mon, Sep 26, 2016 at 4:32 AM, ashutosh srivastava <ashu4487 at gmail.com
> >
> > wrote:
> >
> > > Dear all
> > >
> > > I have performed a 200 ns simulation on a protein ligand  (MOL) system
> in
> > > gromacs 5.1.2. Is it possible to get low frequency motions of only the
> > > ligand?
> > > When I am looking at the filtered trajectory (along PC1) after
> performing
> > > PCA on the protein+MOL the small molecule looks distorted. There is an
> > > aromatic ring in the molecule that collapses and expands during the
> > course
> > > of trajectory and the methyl groups are all collapsed throughout the
> > > trajectory.
> > > Following is the command that I am using
> > >
> > > covar -f "\$TRAJ" -s "\$TPR" -o
> > > ck2_go289_eigval_\${first_frame}_\${interval}.xvg -v
> > > ck2_go289_eigvec_\${first_frame}_\${interval}.trr -av
> > > ck2_go289_eigavg_\${first_frame}_\${interval}.pdb -l
> > > ck2_go289_eiglog_\${first_frame}_\${interval}.log -ascii
> > > ck2_go289_eigcovar_\${first_frame}_\${interval}.dat -xpm
> > > ck2_go289_eigcovar_\${first_frame}_\${interval}.xpm -xpma
> > > ck2_go289_eigcovara_\${first_frame}_\${interval}.xpm -b \$first_frame -e
> > > \$interval
> > >
> > > anaeig -v ck2_go289_eigvec_\${first_frame}_\${interval}.trr -f "\$TRAJ"
> -s
> > > "\$TPR" -eig ck2_go289_eigval_\${first_frame}_\${interval}.xvg -comp
> > > ck2_go289_eigcomp1_\${first_frame}_\${interval}.xvg -rmsf
> > > ck2_go289_eigrmsf1_\${first_frame}_\${interval}.xvg -proj
> > > ck2_go289_eigproj1_\${first_frame}_\${interval}.xvg -filt
> > > ck2_go289_eigfilt1_\${first_frame}_\${interval}.xtc -first 1 -last 1 -b
> > > \$first_frame -e \$interval
> > >
> > > I have also tried giving -extr option and the extracting 2000 frames
> > along
> > > the PC1, the molecule looks distorted even in this.
> > >
> > > I have tried following
> > > 1) Fitting CA and MOL and covariance analysis on CA and MOL
> > > 2) Fittting CA only and covariance on MOL only
> > > 3) Fitting MOL only and covariance on MOL only
> > > 4) Isolating the MOL trajectory separately and then performing PCA on
> > this
> > > trajectory.
> > > 5) Fitting all atoms and covariance analysis on all atoms
> (protein+MOL).
> > >
> > > Before all this I performed following PBC corrections on the
> trajectory.
> > >
> > > trjconv -s prod_0-10.tpr -f prod_0-100.xtc -o whole_100ns.xtc -pbc
> whole
> > >
> > > trjconv -s prod_0-10.tpr -f whole_100ns.xtc -o nojump_100ns.xtc -pbc
> > nojump
> > >
> > > trjconv -s prod_0-10.tpr -f nojump_100ns.xtc -o
> center_mol_ur_compact.xtc
> > > -pbc mol -center -ur compact -n index.ndx
> > >
> > > trjconv -s prod_0-10.tpr -f center_mol_ur_compact.xtc -o
> > > fit_center_mol_ur_compact.xtc -n index.ndx -fit rot+trans
> > >
> > > I have done mass weighted analysis and the result is the same.
> > > In all the cases the MOL becomes distorted in the filtered trajectory.
> > > In order to visualize the trajectory I am extracting the 0th frame of
> the
> > > trajectory (CA and MOL) from the actual trajectory and then loading
> > > filtered trajectory on top of that.
> > > I also tried extracting the 0th frame of filtered trajectory and then
> > > I have looked at the actual trajectory  and the small molecule as well
> as
> > > protein is fine in that with no weird motions.
> > >
> > > What am I doing wrong here?
> > >
> > > Kindly let me know if anymore details are required.
> > >
> > > Thank you
> > >
> > > Ashutosh.
> > > --
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> >
> >
> >
> > --
> > Tsjerk A. Wassenaar, Ph.D.
> > --
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--
Tsjerk A. Wassenaar, Ph.D.
```