[Dock-fans] positive energy with water molecule

[Scott Brozell]

Hi,

On Thu, 11 Sep 2008, Anuradha Mittal wrote:

> Thanks for the suggestion.
> 
> 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
> 
> There was not much change in receptor energy in all the cases. But complex
> energy varied a lot. I believe if clashes due to water were the cause, then
> there should had been a low amber score when one of the waters was removed.
> And clashes within the protein should show up in all the cases.

Yes that is likely.
Which energy terms in the verbose outputs for the complexes
cause the changes ?

Scott


> On Wed, Sep 10, 2008 at 7:15 PM, Scott Brozell <sbrozell at scripps.edu> wrote:
> > 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   9383  CD  GLN   612       2.411  -7.714  89.480  1.00  0.00
> > > ATOM   9384  OE1 GLN   612       2.171  -8.868  89.108  1.00  0.00
> > > ATOM   9385  NE2 GLN   612       1.788  -6.653  88.977  1.00  0.00
> > > ATOM   9386 1HE2 GLN   612       1.089  -6.775  88.258  1.00  0.00
> > > ATOM   9387 2HE2 GLN   612       2.016  -5.729  89.316  1.00  0.00
> > > ATOM   9388  C   GLN   612       3.390  -5.182  93.653  1.00  0.00
> > > 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 ?
> >
> > Scott
> >
> > > But there is no atom number 9434 and 9437 in pdb. Also, 9390 is not C,
> > but O
> > > of terminal Gln.
> > >
> > > There are no other errors in dock6 log file.
> > >
> > > On Tue, Sep 9, 2008 at 1:10 AM, Scott Brozell <sbrozell at scripps.edu>
> > wrote:
> > >
> > > > 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.
> > > > >
> > > > > I am getting positive amber score for all the ligands. However if I
> > > > remove
> > > > > that water molecule all scores are negative. I prepared all
> > structures
> > > > using
> > > > > sybyl but did change the nomenclature according to amber.
> > > >
> > > > What exactly does this mean ?
> > > > Did you execute prepare_amber.pl ?
> > > > If a water exists in the receptor pdb file argument to prepare_amber.pl
> > > > then a TIP3P water model will be used.  So if the pdb has, e.g.,
> > > > TER
> > > > ATOM  30277  O   WAT  9659       0.444  -0.413 -43.191  1.00  0.00
> > > > ATOM  30278  H1  WAT  9659      -0.232  -0.514 -42.521  1.00  0.00
> > > > ATOM  30279  H2  WAT  9659       1.267  -0.569 -42.727  1.00  0.00
> > > > then the prmtop will have a WAT residue.
> > > >
> > > > > What am I doing wrong here? Is it that Amber-dock doesn't support
> > water
> > > > > molecules? Or do I need to explicitly define the parameters for
> > water?
> > > > Any
> > > > > suggestions?
> > > >
> > > > Since there is a change in the Amber rescores with and without water,
> > > > the water seems to be there.  The simple diagnostic route starts with
> > > > visualization, and probably the extra details from verbose dock6 (-v)
> > > > calculations will be informative.  The most likely source of the
> > positive
> > > > energy is a clash which should show up in both of the above, but the
> > phase
> > > > space of possibilities is large.