ADL: Modelling water
Garrett M. Morris
garrett at scripps.edu
Wed Sep 8 15:04:52 PDT 2004
On Sep 8, 2004, at 7:53 am, Bhatia, Smita wrote:
> Hi everyone,
> The ligand binding site in my protein has 2 water molecules that could
> interacting with the ligand. How can I use autodock to model these
You can treat the waters as part of the protein, then compute a set of
grid maps around the protein + water combination, but first you must
add their hydrogens. Placement of the hydrogens is particularly
important for Thr, Ser and Tyr hydroxyls, as well as waters, of course.
Some PDB structures could also form better hydrogen bond networks if
an Asn or Gln side chain's terminal O=C-NH2 groups are flipped
(presumably because the electron density map couldn't unambiguously
indicate which heteroatom is which).
A related point to consider is the protonation state of all your
ionisable side chains: this will be determined by the pH and salt
concentrations, and you should look into pKa calculations: there is a
nice introduction at:
along with a list of software
You will need to place the hydrogens in a reasonable place. There are
at least 4 options:
(1) Use AutoDockTools to add hydrogens.
(2) You can use InsightII's Discover, AMBER, CHARMM, GROMOS, VMD or any
other molecular mechanics/dynamics package to minimize the energy of
the system, but remember to fix the heavy atom positions and just
optimise the positions of the hydrogens.
(3) Alternatively, you could use WHAT-IF's WHAT_CHECK.
R.W.W. Hooft, G. Vriend, C. Sander, E.E. Abola, "Errors in protein
structures." Nature, 381, 272-272 (1996).
(4) A fourth option is you could use the PDB2PQR web server through
APBS portal. This can optimize the protein hydrogen network (but can
significantly increase computational time); and if you do this, you can
choose to optimize the water hydrogen network. See:
Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA. "PDB2PQR: an automated
pipeline for the setup, execution, and analysis of Poisson-Boltzmann
electrostatics calculations." Nucleic Acids Research 32 W665-W667
Remember we treat the protein with the United Atom model, which means
we keep polar hydrogens; the non-polar hydrogens (attached to carbons)
can be "merged" using AutoDockTools. Merging means we add the partial
charge from the hydrogen to that of the carbon it is bonded to, then
delete the hydrogen.
I hope this helps,
> I also think that Autogrid will have to be changed so it would
> consider an
> oxygen bound to 2 hydrogens as a potential bond acceptor, allowing for
> correct treatment of water molecules. Can anyone suggest how to do
AutoGrid can properly handle waters in the protein.
> Thanks a lot,
> Smita Bhatia
> Institute for Biological Sciences
> National research Council
> 100-Sussex Drive, Room # 3031
> Ottawa, ON K1A 0R6
> Phone: (613)990-0855
> Email : Smita.Bhatia at nrc-cnrc.gc.ca
> <mailto:Smita.Bhatia at nrc-cnrc.gc.ca>
> --- ADL: AutoDock List ---
> http://www.scripps.edu/pub/olson-web/doc/autodock/ ---
Dr Garrett M. Morris, MA, DPhil
The Scripps Research Institute, tel: (858) 784-2292
Dept. Molecular Biology, MB-5, fax: (858) 784-2860
10550 North Torrey Pines Road, email: garrett at scripps.edu
La Jolla, CA 92037-1000, USA. www.scripps.edu/pub/olson-web/gmm
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