Date: Tue, 07 Nov 2000 15:31:37 -0600
From: Craig Marhefka
Subject: OWFEG documentation

Dear amber users,

Below is a list of the OWFEG namelist options and a sample input file that
should allow those of you who wish to do these calculation to do so. I also
have attached a word copy of the document.

In order to run OWFEG calculations one adds an &ligrid namelist
(terminating with an &end) after the &cntrl namelist in the sander_classic
in put file.

One should refer to, “Free Energy Grids : A Practical Qualitative
Application of Free Energy Perturbation to Ligand Design Using the OWFEG
Method” by David Pearlman in J. Med. Chem. 1999, 42, 4313-4324., for more
detail and a description of the method.

The descriptions below are from David Pearlmans comments, with slight
modification, in the lgcom.h file in the sander_classic source directory of
the AMBER6 distribution.



Craig A. Marhefka


&ligrid namelist options:


RADLG: Radius to be used for the probe particle on the grid. Default = 2.0

EPSLG: Epsilon to be used for the probe particle on the grid. Default = 0.15

RLGDIS: Maximum distance from any grid point to any ligand atom on setup to define
the extent of the grid about the ligand. Default = 3.0

RLGEXC: Minimum distance from any grid point to any ligand atom on setup to define
closest allowed grid points. Default = 1.0

RLGSPC: Spacing of the grid about the ligand. Default = 1.0

CHGPRB: Value of the probe charge. If > 0, then free energies will be calculated for
charged particles with + and - CHGPRB, as well as for an uncharged particle.
Default = 0.0

RTOLCS: If any grid point is closer than RTOCLS Å from any atom, the non-bonded
interaction will be set to BIGCLS and the electrostatic interaction will be set
to 0. Only used if CHGPRB >0. Default = 0.5

BIGCLS: Value of non-bonded interaction to be used if ligand grid position is too
close to real atom as defined by RTOLCS . Only used if CHGPRB > 0.
Default = 1000

RLGREP: If > 0, then any the free energy at any grid point that is < RLGREP Å from
an atom of the ligand will be calculated from a reference state of the closest
ligand atom, rather than as a reference state of "nothing". If RLGREP is < 0
free energy at any grid point that is < | RLGREP | be calculated from the atom
reference state ONLY if closest atom is a hydrogen. Default = 0

XLGMM (1- 6): Optional limits in X,Y, and Z directions. If specified then in addition to
all other criteria, ligand grid points cannot fall outside of the
rectangular box defined by xlow = XLGMM(1), xup = XLGMM(2),
ylow = XLGMM(3), yup = XLGMM(4), zlow = XLGMM(5), zup =
XLGMM(6). Default = 0.0

RLGDI2: If specified > 0, then a second set of coordinates will be read from LGSETR, and additional to any other criteria in generating grid points, grid points
must also be withing RLG2ST Å of an atom in LGSETR. Allows
one to force a grid to be localized to the region about a known inhibitor
when that inhibitor is not actually in the molecular system being used.
Default = 0

RLGEX2: If RLGDI2 and a second set of coordinates being used to limit the grid,
RLGEX2 gives the minimum distance allowed to any atom in the second set
of coords. (Can set <0 to turn of this check). Default = 0

LGLIG1: Atom number in topology file which corresponds to the first ligand atom.
Default = 0

LGLIG2: Atom number in topology file which corresponds to the last ligand atom.
Default = 0

LGLIG3: If one wishes to specify a subset of atoms within the ligand to limit grid
generation about this subset, LGLIG3 is the atom number in the topology file
that corresponds to the first atom of the subset. Default = 0

LGLIG4: LGLIG4 is the atom number in the topology file that corresponds to the last
atom of the subset. Default = 0
All atoms of the ligand are still used to define the excluded space (RLGEXC).

LGREST: = 0 if not a restart run (Default)
= 1 if a restart run

LGSKP: Number of steps of MD to skip (i.e. equilibration) before starting to
accumulate free energy grid info. Default = 0

LGWRIT: Ligand restart file written every LGWRIT steps. Default = 1000

LGCOR: = 0 ligand reference coordinates taken from standard input coordinates
= 1 ligand reference coordinates taken from file LGREF
(must contain only
ligand atoms and in same order as topology)
= 2 ligand reference coordinates taken from LGRSFI
(default if LGREST =
1, otherwise 0 is default).

LGHIGN: = 0 no affect (Default)
= 1 ignore hydrogen atoms when determining the positions of ligand grid
atoms using rlgdis and rlgexc

LGIGR1 and LGIGR2 :
If LGIGR1 > 0, then ignore the range of atoms LGIGR1 - LGIGR2 when
calculating the non-bonded interactions of the grid points with the system.
The special case LGIGR1 = -1 will result in setting LGIGR1 = LGLIG1 and
LGIGR2 = LGLIG2. Default = 0

LGATRF: By default (LGATRF=0), the program determines the closest atom of the
ligand to each grid point and uses that to determine the reference frame for
that grid point. If LGATRF > 0, then atom LGATRF is used to define the
reference frame for all atoms. Setting LGATRF caused a PROFEC type
calculation.


LGEXCL: By default (LGEXCL=0), the pairlist for the closest atom to each ligand grid
point is used, obeying any non-bonded exclusions to that
atom. If ILGEX > 0,
then the non-bonded exclusions list for that atom is ignored. This is useful if
one is generating the free energy grid about a group that one does not expect
to covalently bond to.


The following namelist flags are set to string values which should be in
single or double quotes.

KGFIL: Name of the file to be used to output the ligand grid data.

KGRSFO: Name of the file to be used to output the ligand restart data.

KGRSFI: Name of the file to be used to input the ligand restart data.

KGREFC: Name of optional file to be used to input the reference ligand
coordinates.

KGSETR: Name of optional file (only used if RLGDI2>0) to be used in limiting the
extent of the grid.


A sample input file:

&cntrl
imin=0,nmropt=0, scee=1.2,
ntx=7,irest=1,
ntpr=1, ntwr=100,
ntwx=10,ntwv=0,ntwe=10,ntwprt=0,
ntwxm=0,ntwvm=0,idiel=1,
ntf=2,ntb=2,dielc=1,cut=10,cut2nd=12,nsnb=20,
ibelly=0,ntr=0,
nstlim=50000,ndfmin=0,ntcm=1,nscm=1000,init=4,dt=0.002,
temp0=300,tempi=0,ig=14298,ntt=1,tautp=0.5,
ntp=1,taup=0.2,npscal=1,
ntc=2,tol=0.0000001,

&end
&ligrid
radlg=2.0, epslg=0.15, rlgdis=3.0,
rlgexc=1.4, rlgspc=0.5, chgprb=0.3,
rtocls=0.5, rlgrep=0, lglig1=1,lglig2=31,
lgrest=0,lgskp=0,lgwrit=500,lgcor=0,
lghign=1, lgigr1=0,lgigr2=0,lgatrf=0,lgexcl=0,
kgfil= 'lgfil', kGRSFO= 'lgrsfo' , kGRSFI= 'lgrsfi' ,
KGREFC= 'lgrefc' , KGSETR= 'lgsetr' ,
&end





Content-type: application/msword; name=OWFEG.doc
Content-disposition: attachment; filename=OWFEG.doc
Content-comments: Conversion error: %NONAME-W-NOMSG, Message number 00000000

Attachment Converted: "c:\eudora\attach\OWFEG.doc"