AMBER Archive (2002)

Subject: solvating a protein with large cavity

From: Tom Bishop (bishop_at_tulane.edu)
Date: Sat Dec 14 2002 - 09:42:38 CST

Dear amber,
I'm trying to solvate a protein w/ a large cavity (~500A^3) using tleap
in amber7.
Since a single water is about 30A^3 large I would expect somewhere
between 15-20 waters to be located in the cavity.
Simply using solvatebox does not put any waters in the cavity, but fills
up a box as one would normally expect.

Here's the tleap input.

source leaprc.ff99
REC = loadpdb pro.pdb
solvatebox REC WATBOX216 6
set default OldPrmTopFormat on
saveAmberParm REC vmd.top tmp.crd
set default OldPrmTopFormat off
saveAmberParm REC rec-wat.top rec-wat.crd
savepdb REC amberout.pdb
quit

tleap does not report any errors, missing atoms, problems etc....It adds
a bunch of water and
looking at the output I see there is a box of water added to the system,
but the cavity is empty!
tleap output is attached below at the end

I then tried to use solvatecap. First I identified the amino acids which
make up the "boundary" of the cavity, assuming
the geometric center of these a.a. would be a good estimate of position
of the cavity, but solvatecap is apparently not determining the center
of geometry for these selected a.a. as the manual says it should. This
may be a syntax problem on my part, but
I looked thru the manual to find out what a "container" is and didn't
see anything.

Here is the tleap input
source leaprc.ff99
  REC = loadpdb pro.pdb
  CAPRES = { REC.39 REC.42 REC.45 REC.73}
## only a partial list of a.a. is given here b/c the actual list is very
long
## just to see how things are working
   desc CAPRES
## all looks OK
   center CAPRES
## gives {0,0,0} apparently CAPRES is not a valid arguement to center.
## so let's not use it for solvatecap either :-)
solvatecap REC WATBOX216 { REC.39 REC.42 REC.45 REC.73} 6
set default OldPrmTopFormat on
 saveAmberParm REC vmd.top tmp.crd
set default OldPrmTopFormat off
 saveAmberParm REC rec-wat.top rec-wat.crd
 savepdb REC amberout.pdb
 quit

Amber does succesfully add some water to this system, but it's a small
ball of water with radius 6A located at the origin.
That would be fine if the center of the cavity were at the origin, but
the 6A ball of water is not touching the protein
since the center of mass of the protein is located about 15A from the
origin for the coordinate set that I"m using.

Any suggestions on how to fill this cavity in the protein?
Any suggestions on how to call solvatecap with a list of residues would
be greatly appreciated even if doesn't apply to this particular problem.

Thanks,
TOm

leap.log contents, partial listing only

 Sequence:
  Sequence: TP3
> solvatebox REC WATBOX216 6
  Solute vdw bounding box: 67.175 59.247 50.375
  Total bounding box for atom centers: 79.175 71.247 62.375
  Solvent unit box: 18.774 18.774 18.774
The number of boxes: x= 5 y= 4 z= 4
Adding box at: x=0 y=0 z=0
Center of solvent box is: 37.548698, 28.161524, 28.161524
Adding box at: x=0 y=0 z=1
Center of solvent box is: 37.548698, 28.161524, 9.387175
Adding box at: x=0 y=0 z=2
Center of solvent box is: 37.548698, 28.161524, -9.387175
Adding box at: x=0 y=0 z=3
Center of solvent box is: 37.548698, 28.161524, -28.161524
Adding box at: x=0 y=1 z=0
Center of solvent box is: 37.548698, 9.387175, 28.161524
Adding box at: x=0 y=1 z=1
Center of solvent box is: 37.548698, 9.387175, 9.387175
etc...
etc..
etc..
Center of solvent box is: -37.548698, -28.161524, -9.387175
Adding box at: x=4 y=3 z=3
Center of solvent box is: -37.548698, -28.161524, -28.161524
  Total vdw box size: 82.086 74.160 65.657 angstroms.
  Volume: 399688.851 A^3
  Total mass 191580.364 amu, Density 0.796 g/cc
  Added 9087 residues.
> set default OldPrmTopFormat on
> saveAmberParm REC vmd.top tmp.crd

and for the solvate cap part of things

> solvatecap REC WATBOX216 { REC.39 REC.42 } 6
The number of boxes: x= 1 y= 1 z= 1
Adding box at: x=0 y=0 z=0
Center of solvent box is: 0.000000, 0.000000, 0.000000
Added 23 residues.
> set default OldPrmTopFormat on
> saveAmberParm REC vmd.top tmp.crd 

-- 
-----------------------------------------
Thomas C. Bishop, Ph.D.
Joint Faculty Appointments Program Professor
Center for Bioenvironmental Research
-----------------------------------------
Tulane University Office
-----------------------------------------
Dept. of Environmental Health Sciences(SL-29)
School of Public Health & Trop. Medicine
1430 Tulane Avenue
New Orleans, LA 70112
Phone: 504-988-6203   Fax: 504-585-6428 
bishop_at_tulane.edu
-----------------------------------------
Xavier University Office
-----------------------------------------
Division of Basic Pharmaceutical Sciences
College of Pharmacy
7325 Palmetto Street
New Orleans, LA 70125
Phone: 504-485-5106   Fax: 504-485-7954
tbishop_at_xula.edu
-----------------------------------------