Help/suggestions needed with PROFEC

From: Salinthip Thipayang <>
Date: Fri 03 May 2002 15:40:41 +0100

Dear AMBER users,

If anyone has any idea or has any
experiences in using PROFEC please take
a minute to look at this email. I posted
an email to AMBER mail reflector archive
before ( which is the email that I also
attach at the end of this message) but I
have got no reply at all. So if there
are still PROFEC users out there, even
if you cannot solve my problems, could
you please just reply so that I know
there are still some people using PROFEC
like me.

I have 2 questions that I really need
the suggestions/answers/recommendations
from you.

My first question is when I run this
command line:

cat <.crd file> |
<> <.prm file> <.rst file>

which (in my understanding) is
equivalent to the command line given in
PROFEC manual:

cat <traj> | makeGrid <in> <top> <crd>
<ljp> <vdw> <esp> <obj> <sav>

where <.crd file> is my coordinate file
from MD run using SANDER6
               <> is the
input file as given in the example in
the manual
               <.prm file> is the parm
topology file created by XLEAP
               <.rst file> is the
restart file after the MD run (same MD
run that produced the <.crd file>
specified before) using SANDER6

Note that there is no makeGrid program,
instead it is profec_grid in the
/usr/local/amber6/exe/ directory. This
is exactly the same quesion that Anna
Ferrari posted in the mailing list on

I got the following error message:

        3 1
makeGrid in top crd ljp vdw esp obj sav

( I am not sure if the numbers 3 and 1
above the actual message is refering to
the positions of the file
and <.rst file> from my command line)

>From my understanding I think I only
need to put 4 inputs i.e. 1) the <.crd
file> 2) 3) <.prm file> and
4) <.rst file> in the profec_grid
command line in order to get the outputs
<lpj>, <vdw>, <esp>, <obj> and <sav>
out. These output files will then be
used in makeDiffGrid and Field (with
Midas) to qulitatively calculate the
ddGbind and to view the grid
respectively. Please correct me if I
understand wrongly about this.

My second question (which is not really
valid at this stage unless I can get the
makeGrid command to work first) is that
how would one define the R* (van der
Waals radius) and the epsilon (van der
Waals well depth) used in the as Rprobe and Eprobe values
respectively? Say if I want to change
the COO- (carboxyl) group in GLU residue
in the native enzyme to other group
such as CH3, NH2 etc. in the mutant
enzyme, what are the values of R* and
epsilon to use here? Do I use the atomic
carbon van der Waal parameters for atom
type C of the carboxyl or carbonyl
carbon (1.9080, 0.0860 as in parm98.dat
file) or do i need to use values for the
united atom model for COO- group? The
example of the file in the
PROFEC manual seems to use Rprobe=
1.9080 and Eprobe= 0.1094 (taken from
parm98.dat) which are for the sp3 carbon
atom typeCT; whereas the two references
that I quoted in my previous email (L.
Wang et al 1998 and R.J. Radmer and P.A.
Kollman 1998) seem to use the united CH3
atom with values of R*= 2.0 A and
epsilon=0.15 kcal/mol. These values seem
to be taken from table XIX on page 781
of S.J. Weiner et al, J. Am Chem. Soc.,
1984, 106. 765-784 which shows the R*
and epsilon values for nonbonded

Thank you very much for spending some of
your time reading/ replying this email.
Your help/ suggestions/ recommendations
are really appreciated. Thank you very
much again.

Yours Sincerely,

Salinthip Thipayang

The following is my previous email that
I posted on 19/04/2002

Dear PROFEC users,

I am trying to use PROFEC to
qualitatively predict the effect of
changing the residue in the binding site
of a protein from the free energy
calculations obtained
from PROFEC. The first step of using
PROFEC ( as I understand from the
manual) is to make particle grids (van
der Waals and electrostatic) for the
protein-ligand and for ligand-water
systems, using the makeGrid file (or
profec_grid in AMBER6). The manual
describes the command line as:

cat <traj> | makeGrid <in> <top> <crd>
<ljp> <vdw> <esp> <obj> <sav>

I understand that cat <traj> is obtained
from the mdcrd file as obtained by
SANDER. makeGrid <in> is the input
command file which is briefly described
and an
example is given in the manual. <top> is
the AMBER topology file as obtained in
Xleap. <crd> is the mdcrd file contained
coordinate references and can be
obtained by Xleap. But how and where
can I obtain the <vdw>, <esp>, <obj> and
<sav> files? What programs do I have to
use to get them? The manual
descibes what they are but does not say
how are they calculated and what
programs required to get these files to
generate the grids. I notice the second
after the makeGrid process is the
makeDiffGrid and we need to generate the
<protein.vdw>, <solvent.vdw>,
<output.vdw>, <protein.esp> etc. Anther
question is how can one generate these
<protein.vdw>, <solvent.vdw>?

I have read the quoted references about
PROFEC e.g. from

R.J.Radmer and P.A.Kollman, 'The
application of three approximate free
energy calculations methods to structure
based ligand design: Trypsin and its
with inhibitors', J. Computer-Aided Mol.
Design, 12: 215-227, 1998.

L.Wang, 'Can one predict protein
stability? An attempt to do so for
Residue 133 of T4 Lysozyme using a
combination of free energy derivatives,
and free energy perturbation methods',
Proteins: Structure, Function and
Genetics 32: 438-458, 1998.

M.A.L.Eriksson, 'Prediction of
the binding free energies of new
TIBO-like HIV-1 reverse transcriptase
inhibitors using a combination of
PB/SA, CMC/MD, and free energy
calculation', J. Med. Chem., 42:
868-881, 1999

These references are very useful but
they do not describe the methods of
using PROFEC in terms of the
computational set up details. If there
are any other
references that you think may be useful,
please quote them as well.

Any comments, any recommendation will be
greatly appreciated. Thank you everyone
in advance for spending time reading/
replying this email.

I really hope to get some reply please!

Yours sincerely,

Salinthip Thipayang

Salinthip Thipayang (Miss)
PhD Research Student
Biological and Biophysical Chemistry Research Group
Chemistry Department
Imperial College of Science, Technology and Medicine
Exhibition Road
London SW7 2AY
The United Kingdom
Tel: +44(0)207 5945851
Fax: +44(0)207 5945845
Received on Fri May 03 2002 - 07:40:41 PDT
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