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

ashutosh srivastava ashu4487 at gmail.com
Mon Sep 26 11:10:07 CEST 2016

```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
> > loading the trajectory on top of that.
> > 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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```