grid (c46b2)

Grid: A general facility to implment grid-based potentials for docking


# Charles L. Brooks III, TSRI. December 2000.


This document node describes the implementation, commands and syntax
associated with an implementation of grid-based potentials to be used
in ligand-docking studies, or when an additional set of potentials are
to be added to augment. It can be used with dynamics as well as the
GA/MC module.

* Implementation | A brief description of the anatomy of the module
* Syntax | Syntax of the commands
* Description | Description of key words and commands usage
* Restrictions | Restrictions on usage
* Examples | Supplementary examples of the use of the module


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Grid-based potentials: Description and Discussion


energy/energy.src, energy/eutil.src, energy/intere.src,
energy/printe.src, charmm/iniall.src, charmm/charmm_main.src

This module provides code to 1) generate a set of van der Waals and
electrostatic grid-based potentials and to 2) use these potentials in
dynamics, minimization and GA/MC-based searching algorithms.

Generation of the grid-based van der Waals potentials is accomplished
by establishing a series of vdW radius based potential surfaces over a
limited spatial extent specified by the user. This set of potentials
is built for radii of a series of test particles of unit epsilon
parameter. The general idea is to use radii that span the range of
radii used in the force field of interest, either on a discrete grid
or at particular values. In utilizing these grids for energy and force
calculations, the vdW radius of the atoms in the target molecule are
mapped to the nearest probe radius, with a warning being given if the
radii differ by more than 0.1 A, and the overall energy is scaled by
the square-root of the specific atoms vdW epsilon. This simplification
provides a means to minimize the number of 3D grids that must be
generated to represent the potential for a complex system. However, if
memory is not an issue, in principle grid-based potentials may be
generated for all vdW-based atom radii.

The electrostatic-based potential is the electrostatic potential
associated with a test charge throughout the user specified space.

The potential energy is computed as a 3D, 8-point linear interpolation
with forces computed from the analytic gradient of this interpolation
formula. The potential energy and forces beyond the grid edges is
constructed as a quadric potential away from the grid edge.

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Syntax for the Grid-based potentials

Generation:

grid generate select <atom selection> end -
[xcen <real>] [ycen <real>] [zcen <real>] -
[xmax <real>] [ymax <real>] [zmax <real>] -
[dgrid <real>] [Force <real>] -
[OutUnit <integer>] [Formatted] [Print]

Initiailization:

grid read select <atom selection> end -
Unit <integer> [Formatted] [Print]

grid on select <atom selection> end

grid off

grid clear


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There are two basic parts to utilizing grid-based potentials in CHARMM:

Description of the basic key words for grid-based potentials:

The following is the description of the setup commands for setting up the
system

Keyword/Syntax Default Purpose

GENErate Setting up the data structure and calculating
the potential grids.

READ Keyword to read a set of grid-based potentials
and set-up grid-based energy calculations.

ON Keyword to activate grid-based potential
calculations.

OFF Keyword to de-activate grid-based potential
calculations.

CLEAr Keyword to clear all grid-based potential
data structures from heap and stack.

XCEN 0.0 (A) X-position for center of grid-based potentials.

YCEN 0.0 (A) Y-position for center of grid-based potentials.

ZCEN 0.0 (A) Z-position for center of grid-based potentials.

XMAX 0.0 (A) X-direction extent of the potential grid.

YMAX 0.0 (A) Y-direction extent of the potential grid.

ZMAX 0.0 (A) Z-direction extent of the potential grid.

DGRId 0.5 (A) Spacing between consequetive points in
potential grids.

FORCe 300.0 Force constant for quadratic extention of
potential beyond grid edges, in kcal/mol/A^2.

OUTUnit Std Out Unit to write grid-based potential file.

UNIT Std Out Unit from which to read grid-based potential file.

FORMatted .false. Logical to set reading/writing of grid-based
potentials in ascii format.

PRINt .false. Logical to set whether grid-based potentials
will be printed to standard out.


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This module is in alpha release and subject to change. All aspects
should work but this energy term has not been implemented in all other
pert, tsm or block, or with the MC module of Arron Dinner.


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Supplementary examples.

Generate and test grid for simple example of test atom.
probes.RTF:
* ...

22 0
MASS 301 P1 1.00 P1 !
MASS 302 P2 1.00 P2 !
MASS 303 P3 1.00 P3 !
MASS 304 P4 1.00 P4 !
MASS 305 P5 1.00 P5 !
MASS 306 P6 1.00 P6 !
MASS 307 P7 1.00 P7 !
MASS 308 P8 1.00 P8 !
MASS 309 P9 1.00 P9 !
MASS 310 P10 1.00 P10 !
MASS 311 P11 1.00 P11 !
MASS 312 P12 1.00 P12 !
MASS 313 P13 1.00 P13 !
MASS 314 P14 1.00 P14 !
MASS 315 P15 1.00 P15 !
MASS 316 P16 1.00 P16 !
MASS 317 P17 1.00 P17 !
MASS 318 P18 1.00 P18 !
MASS 319 P19 1.00 P19 !
MASS 320 P20 1.00 P20 !

RESI PROB 20.000
ATOM P1 P1 1.0 p2 p3 p4 p5 p6 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P2 P2 1.0 p3 p4 p5 p6 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P3 P3 1.0 p4 p5 p6 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P4 P4 1.0 p5 p6 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P5 P5 1.0 p6 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P6 P6 1.0 p7 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P7 P7 1.0 p8 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P8 P8 1.0 p9 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P9 P9 1.0 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P10 P10 1.0 p11 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P11 P11 1.0 p12 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P12 P12 1.0 p13 p14 p15 p16 p17 p18 p19 p20
ATOM P13 P13 1.0 p14 p15 p16 p17 p18 p19 p20
ATOM P14 P14 1.0 p15 p16 p17 p18 p19 p20
ATOM P15 P15 1.0 p16 p17 p18 p19 p20
ATOM P16 P16 1.0 p17 p18 p19 p20
ATOM P17 P17 1.0 p18 p19 p20
ATOM P18 P18 1.0 p19 p20
ATOM P19 P19 1.0 p20
ATOM P20 P20 1.0
END

probes.prm:
* Test probes for grid potential set-up


NBONDED NBXMOD 5 ATOM RDIEL SWITCH VATOM VDISTANCE VSWITCH -
CUTNB 999 CTOFNB 999 CTONNB 999 EPS 3 E14FAC 0.5 WMIN 1.5

! EMIN Rmin These columns used for
! (kcal/mol) (A) 1-4 interactions

P1 0.00 -1.0000 0.65
P2 0.00 -1.0000 0.75
P3 0.00 -1.0000 0.85
P4 0.00 -1.0000 0.95
P5 0.00 -1.0000 1.05
P6 0.00 -1.0000 1.15
P7 0.00 -1.0000 1.25
P8 0.00 -1.0000 1.35
P9 0.00 -1.0000 1.45
P10 0.00 -1.0000 1.55
P11 0.00 -1.0000 1.75
P12 0.00 -1.0000 1.85
P13 0.00 -1.0000 1.95
P14 0.00 -1.0000 2.05
P15 0.00 -1.0000 2.15
P16 0.00 -1.0000 2.25
P17 0.00 -1.0000 2.35
P18 0.00 -1.0000 2.45
P19 0.00 -1.0000 2.55
P20 0.00 -1.0000 2.65

END


* GRIDTEST.INP
* This test-case demonstrates features of the grid-based potentials.
* It utilizes the MSI CHARMm (Momany & Rone) force field and the
* trypsin/benzamidine receptor/ligand pair.
* Required files: MASSES.RTF, probes.RTF, AMINO.RTF, PARM.PRM, probes.prm
* 3ptb_complex.psf, 3ptb_complex.pdb


open unit 1 read card name "MASSES.RTF"
read rtf card unit 1

open unit 1 read card name "probes.RTF"
read rtf card unit 1 append

open unit 1 read card name "AMINO.RTF"
read rtf card unit 1 append

open unit 3 read card name "PARM.PRM"
read param card unit 3


open unit 1 read card name "probes.prm"
read param card unit 1 append

open unit 1 read form name "3ptb_complex.psf"
read psf card unit 1

open unit 1 read form name "3ptb_complex.pdb"
read coor pdb unit 1

! Find the center of the binding site
coor stat select resname ptb end
set xcen = ?xave
set ycen = ?yave
set zcen = ?zave

! Remove "real" ligand
delete atom select resname ptb end

! Generate test probe atoms
read sequ card
* title


prob
generate prob setup

! Delete all atoms but single representative for first grid test
delete atom select .not. ( type p15 .or. segid seg1 ) end

! Set-up position of test atom
scalar x set @xcen select segid prob end
scalar y set @ycen select segid prob end
scalar z set @zcen select segid prob end

! Fix receptor atoms
cons fix select segid seg1 end
energy

open unit 3 write form name grid.ascii
title
* Test grid for system


grid generate xmax 1 ymax 1 zmax 1 xcen @xcen ycen @ycen zcen @zcen -
force 300 dgrid 0.5 select segid prob end outu 3 formatted print

grid clear

open unit 3 write unform name grid.bin
title
* Test grid for system


grid generate xmax 1 ymax 1 zmax 1 xcen @xcen ycen @ycen zcen @zcen -
force 300 dgrid 0.5 select segid prob end outu 3 print

grid clear

open unit 3 read form name grid.ascii
grid read unit 3 formatted select type p15 end print
close unit 3

grid clear

open unit 3 read unform name grid.bin
grid read unit 3 select type p15 end print
close unit 3

! Generate positions on grid, vdW and elec should match grid terms
energy inbfrq 0
Calc Xmax = @Xcen + .5
Calc Ymax = @ycen + .5
Calc zmax = @zcen + .5
Calc Xmin = @Xcen - .5
Calc Ymin = @ycen - .5
Calc zmin = @zcen - .5

set x = @xmax
label ix
set y = @ymax
label iy
set z = @zmax
label iz

scalar x set @x select type p15 end
scalar y set @y select type p15 end
scalar z set @z select type p15 end
energy
Calc dvdW = ( ?vdW - ?Grvd ) / ?vdw
Calc delec = ( ?elec - ?Grel ) / ?elec
write title unit 12
* ?Grvd ?Grel ?vdW ?elec @dvdw @delec

Calc z = @z - 0.5
if z ge @zmin goto iz
Calc y = @y - 0.5
if y ge @ymin goto iy
Calc x = @x - 0.5
if x ge @xmin goto ix

! Test on/off components of grid energy terms
grid off
energy

grid on select type p15 end
energy

skipe all excl grvd grel
energy

! Generate energy curve along diagonal of cube to demonstrate interpolation
! and extrapolation.

label dodiagonal
Calc xlow = @Xmin - 0.5
Calc x = @xmax+0.5
Calc y = @ymax+0.5
Calc z = @zmax+0.5
set cnt = 0
skipe all excl elec vdw grel grvd
label diagonal
scalar x set @x select type p15 end
scalar y set @y select type p15 end
scalar z set @z select type p15 end
energy
incr cnt by 1

write title unit 13
* @cnt ?Grvd ?vdW ?Grel ?elec

Calc z = @z - 0.1
Calc y = @y - 0.1
Calc x = @x - 0.1

if x ge @xlow goto diagonal

grid clear

stop

Example 2: An exploration of grid-based potential versus full molecular
potential for benzamidine-trypsin pair.

* GRID_2.INP
* This test-case demonstrates features of the grid-based potentials.
* It utilizes the MSI CHARMm (Momany & Rone) force field and the
* trypsin/benzamidine receptor/ligand pair.
* Required files: MASSES.RTF, probes.RTF, AMINO.RTF, PARM.PRM, probes.prm
* 3ptb_complex.psf, 3ptb_complex.pdb


open unit 1 read card name "MASSES.RTF"
read rtf card unit 1

open unit 1 read card name "probes.RTF"
read rtf card unit 1 append

open unit 1 read card name "AMINO.RTF"
read rtf card unit 1 append

open unit 3 read card name "PARM.PRM"
read param card unit 3

open unit 1 read card name "probes.prm"
read param card unit 1 append

open unit 1 read form name "3ptb_complex.psf"
read psf card unit 1

open unit 1 read form name "3ptb_complex.pdb"
read coor pdb unit 1

! Define dimensions of volume for docking
coor stat select resname ptb end
set xcen = ?xave
set ycen = ?yave
set zcen = ?zave

! Set dimensions of grid as maximum extent of ligand + 4 A
Calc Xmax = ?xmax - ?xmin + 4
Calc Ymax = ?ymax - ?ymin + 4
Calc Zmax = ?zmax - ?zmin + 4
Let Xmax = Max @Xmax @Ymax
Let Xmax = Max @Xmax @Zmax

! If we have already generated the grid potentials go to final part.
! Uncomment after grid generation and run again.
!goto alreadygener

! Remove ligand and generate probe atoms.
delete atom select resname ptb end

read sequ card
* title


prob
generate prob setup

! Set positions for all probe atoms
scalar x set @xcen select segid prob end
scalar y set @ycen select segid prob end
scalar z set @zcen select segid prob end

! Fix position of receptor.
cons fix select segid seg1 end
skipe all excl vdw elec

energy

open unit 3 write unform name grid_3ptb.bin
title
* Test grid for system


! Generate grid-based potentials for 20 probe atoms + electrostatic
! using default grid spacing of 0.5 A and default harmonic potential
! beyond grid edges (300 kcal/mol/A^2).
grid generate xmax @xmax ymax @xmax zmax @xmax -
xcen @xcen ycen @ycen zcen @zcen -
select segid prob end outu 3

grid clear

stop

! Begin here after grid potentials have been generated
label alreadygener

! Fiex receptor atoms for "rigid"-receptor docking
cons fix select segid seg1 end

! Read grid and set-up for ligand (seg2)
open unit 3 read unform name grid_3ptb.bin
grid read unit 3 select segid seg2 end
close unit 3

! Randomly rotate ligand about its center and minimize
Calc phi = ?rand * 30

coor rota xdir @xcen ydir @ycen zdir @zcen phi @phi select segid seg2 end

! Turn off grid potential and minimize using "true" receptor.
grid off
energy inbfrq 1
coor copy compare
mini sd nstep 200 inbfrq 0
coor rms select segid seg2 end

! Turn on grid potential, restore coordinates of ligand and remove receptor
! then minimize using grid-based potential only.
grid on select segid seg2 end
coor swap
coor translate xdir 10000 select segid seg1 end
energy inbfrq 1
mini sd nstep 200 inbfrq 0

! Check rmsd between ligand minimized in actual receptor and in grid-based
! receptor.
coor rms select segid seg2 end

stop