[Dock-fans] positive energy with water molecule

[Scott Brozell]

Hi,

On Tue, 16 Sep 2008, Anuradha Mittal wrote:

> Below is the break up for complex energy for the two cases (with and without
> waters)
> 
> with both waters no waters   bond 434.7848412 405.2092996      angle
> 1389.56007 1374.380492   dihedral 2692.799629 2686.454865      enb14
> 2915.949724 2915.874199      eel14 25828.24525 25828.94577        enb
> -3871.018704 -3893.362396        eel -43353.07493 -43338.01266        egb
> -5257.957187 -5249.77425      econs 0 0      esurf 129.289137 129.4134821
> Total -19091.42218 -19140.8712
> Bond energy and enb are the ones that are most affected.

If I am reading your formatting correctly then
30kcal/mol bond + 22 van der Waals accounts for all of the 50 total
energy change.  This indicates that your waters are highly strained !


> I have another question. Would it be correct if I don't consider the
> absolute score and take the relative ranking. Would this workaround be wise?

Since you indicated that the water is important, there are several 
corrections and workarounds.  It may be ok to merely translate the
Amber scores by ~50kcal/mol (aka relative ranking),
but this workaround is not wise.

The next simplest workaround would be to use an amber_score_movable_region
that includes the waters: either everything or nab_atom_expression;
read the manual carefully to understand the nab_atom_expression:
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#AMBERScore
But the quickest path to a nab_atom_expression that includes only the
water(s) is to use dock6's -v and create an nab_atom_expression
that sets the last strand(s) movable.
As far as everything movable, you could either try various
amber_score_before_md_minimization_cycles
amber_score_md_steps
amber_score_after_md_minimization_cycles
to create a short protocol that mostly merely relaxes the waters
or you could use the resulting blabla.final_pose.amber.pdb
file as a source of better water coordinates.

The best approach would be to obtain a starting receptor pdb file
that has relaxed waters (relative to the TIP3P water model used
in DOCK's Amber score).  There are many ways to do this (in addition
to the shortcut mentioned above).
The obvious one is to run an Amber equilibration calculation; see
http://ambermd.org/tutorials/

Note the new Amber web site link.

Scott

> On Mon, Sep 15, 2008 at 11:43 PM, Scott Brozell <sbrozell at scripps.edu>wrote:
> 
> > On Thu, 11 Sep 2008, Anuradha Mittal wrote:
> >
> > > I used chimera and maestro (from glide) to see bad contacts. But I do not
> > > see any clashes between water/ligand and protein or water and ligand.
> > >
> > > However, I did a small exercise. There are 2 waters in my system, out of
> > > which one is in the ligand binding site. I calculated amber score with
> > both
> > > waters, and keeping one water at a time.  Below are the amber scores:
> > > Both waters: 38.566
> > > Active site water: 40.36
> > > Non active site water: 39.66
> > > No waters: -29.2
> > >
> > Which energy terms in the verbose outputs for the complexes
> > cause the changes ?
> >
> > > On Wed, Sep 10, 2008 at 7:15 PM, Scott Brozell <sbrozell at scripps.edu>
> > > > On Tue, 9 Sep 2008, Anuradha Mittal wrote:
> > > >
> > > > > The prmtop file do has WAT molecule. Below are the last few lines of
> > > > > receptor pdb.
> > > > >
> > > > > ATOM   9389  O   GLN   612       3.491  -4.025  93.202  1.00  0.00
> > > > > ATOM   9390  OXT GLN   612       2.863  -5.448  94.752  1.00  0.00
> > > > > TER
> > > > > ATOM   9391  O   WAT   613       4.178 -24.832 113.225  1.00  0.00
> > > > > ATOM   9392  H1  WAT   613       5.135 -24.832 113.225  1.00  0.00
> > > > > ATOM   9393  H2  WAT   613       3.938 -23.905 113.225  1.00  0.00
> > > > > TER
> > > > > ATOM   9394  O   WAT   614      51.097 -24.833  93.154  1.00  0.00
> > > > > ATOM   9395  H1  WAT   614      52.054 -24.833  93.154  1.00  0.00
> > > > > ATOM   9396  H2  WAT   614      50.857 -23.906  93.154  1.00  0.00
> > > > > TER
> > > > > END
> > > > >
> > > > > The log file from dock6 gives this error:
> > > > >
> > > > > bad number of bonds to C: 9390 1; using default carbon parameters
> > > > > bad number of bonds to O*: 9434 0; using default oxygen parameters
> > > > > bad number of bonds to O*: 9437 0; using default oxygen parameters
> > > >
> > > > Generally, these comments are innocuous.
> > > > Did you visualize the system ?
> > > > Were there high van der Waals energies ?
> > > > In other words, have you verified that clashes are not the source
> > > > of the positive energies ?
> > > >
> > > > > > On Mon, 8 Sep 2008, Anuradha Mittal wrote:
> > > > > >
> > > > > > > I am carrying out amberdock recoring calculations on a set of
> > > > > > > ligands.  There is a water molecule in the protein that
> > > > > > > I need to include while performing the calculations.