AMBER Archive (2000)

Subject: OWFEG documentation

From: Craig Marhefka (cmarhefka_at_utmem.edu)
Date: Tue Nov 07 2000 - 15:31:37 CST

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
Department of Pharmaceutical Sciences
University of Tennessee
847 Monroe Ave. Suite 327
Memphis, TN 38163
e-mail: cmarhefka_at_utmem.edu

&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

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