openmm_dock (c48b2)
OpenMM_DOCK: An Accelerated Routine for Protein-Ligand Docking
Using Parallel MD-based Simulated Anneling on GPUs
By Xinqiang Ding and Charles L. Brooks III
* Background: Background information about the method
* Syntax: Syntax of the command
* Description: Description of the command
* Examples: Example commands
* Installation: How to compile openmm_dock
Using Parallel MD-based Simulated Anneling on GPUs
By Xinqiang Ding and Charles L. Brooks III
* Background: Background information about the method
* Syntax: Syntax of the command
* Description: Description of the command
* Examples: Example commands
* Installation: How to compile openmm_dock
Top
Background Information
This routine is for flexible protein-ligand docking, in which the ligand is
flexible. Part of the protein, usually the amino acid side chains around the
binding pocket can also be modelled as flexible. All the other part of the system
is fixed. Molecular dynamics (MD) based simulated anneling is used to search
for lowes energy conformations. To accelerate the calculation, three tricks are used:
1. The nonbonded interaction between the flexible part and the fixed part are
calculated using grid potentials. (see details in dock.src)
2. A customized OpenMM system consisting of mutiple copies of the flexible part
the protein-ligand complex is employed. Copies of the flexible part are independent,
because there is no interaction between atoms from different copies. Therefore,
runing one trial of simulated annealing with the customized system is equivalent to
running multiple trials of simulated annealing for the protein-ligand complex
3. The MD-based simulated annealing with the customized OpenMM system is run on GPUs
4. Additional two customizable grid potential are added for usage of
introducing hydrogen bond interaction upon binding and potential usage
for covalent docking. (Added in August 2021 By Yujin Wu)
Background Information
This routine is for flexible protein-ligand docking, in which the ligand is
flexible. Part of the protein, usually the amino acid side chains around the
binding pocket can also be modelled as flexible. All the other part of the system
is fixed. Molecular dynamics (MD) based simulated anneling is used to search
for lowes energy conformations. To accelerate the calculation, three tricks are used:
1. The nonbonded interaction between the flexible part and the fixed part are
calculated using grid potentials. (see details in dock.src)
2. A customized OpenMM system consisting of mutiple copies of the flexible part
the protein-ligand complex is employed. Copies of the flexible part are independent,
because there is no interaction between atoms from different copies. Therefore,
runing one trial of simulated annealing with the customized system is equivalent to
running multiple trials of simulated annealing for the protein-ligand complex
3. The MD-based simulated annealing with the customized OpenMM system is run on GPUs
4. Additional two customizable grid potential are added for usage of
introducing hydrogen bond interaction upon binding and potential usage
for covalent docking. (Added in August 2021 By Yujin Wu)
Top
Syntax of Commands
Read Two Grid Potentials:
OMMD GRID UNIS <integer> UNIH <integer> [Formatted]
Create OpenMM System and Context:
OMMD BUILD -
[ SELE <fixed atom selection> END ] -
SELE <flexible atom selection> END -
NCOPY <integer>
[nofi] [GRHB]
Set Positions from Main Coordinates:
OMMD SETC IDXC <integer>
Change the softness of grid potential:
OMMD CGRS -
SOFT <float> HARD <float> -
EMAX <float> MINE <float> MAXE <float> -
EPS <float>
Run Simulated Anneling:
OMMD SIAN -
NSTEP <integer> -
FIRST <float> FINAT <float> TEMI <float> NHRQ <integer> -
FRIC <float>
Copy Position to Main Coordinates
OMMD COOR IDXC <integer>
Syntax of Commands
Read Two Grid Potentials:
OMMD GRID UNIS <integer> UNIH <integer> [Formatted]
Create OpenMM System and Context:
OMMD BUILD -
[ SELE <fixed atom selection> END ] -
SELE <flexible atom selection> END -
NCOPY <integer>
[nofi] [GRHB]
Set Positions from Main Coordinates:
OMMD SETC IDXC <integer>
Change the softness of grid potential:
OMMD CGRS -
SOFT <float> HARD <float> -
EMAX <float> MINE <float> MAXE <float> -
EPS <float>
Run Simulated Anneling:
OMMD SIAN -
NSTEP <integer> -
FIRST <float> FINAT <float> TEMI <float> NHRQ <integer> -
FRIC <float>
Copy Position to Main Coordinates
OMMD COOR IDXC <integer>
Top
Detailed Description of Options in Commands
Read Two Grid Potentials:
OMMD GRID UNIS <integer> UNIH <integer> [Formatted]
UNIS Unit from which to read the soft protein grid potentials
UNIH Unit from which to read the hard protein grid potentials
Formatted Set if the grid potential is in ASCII format
This command reads two grid potentials (soft and hard) for the fixed part of
protein. The grid is generated using grid command (» grid ).
Create OpenMM System and Context:
OMMD BUILD -
[ SELE <fixed atom selection> END ] -
SELE <flexible atom selection> END -
NCOPY <integer>
[nofi] [GRHB]
NCOPY num of copies of flexible atoms
nofi only flexible atoms are used to build the OpenMM system
GRHB The grid energy calculation includes the customizable grids.
Given the fixed atom selection and the flexible atom selection, this command
create an OpenMM system, which comprises of one copy of the fixed atoms and
NCOPY copies of the flexible atoms. When there are no fixed atoms, as
in the case of flexible-ligand and rigid-protein docking, only the flexible atom
selection is specified to be the ligand atoms and nofi option has to be turned on.
When part of the protein is also flexible, the flexible atom selection should include
both ligand atoms and flexible protein atoms and the fixed atom selection should
include the atoms to which the flexible part of the protein connect. During the MD-based
simulated annealing, only the atoms in the flexible atom selection moves. Although
the atoms in the fixed atom selection do not move, they have to be included in the
system such that the flexible part of the protein does not lose bonds with the fixed
part and drift away. This command also creates an OpenMM context with CUDA platform.
Set Positions from Main Coordinates:
OMMD SETC IDXC <integer>
IDXC the index of the copye of flexible atoms whose positions are set based on
the main coordinates.
Change the softness of grid potential:
OMMD CGRS -
SOFT <float> HARD <float> -
EMAX <float> MINE <float> MAXE <float> -
EPS <float>
SOFT <float> a float number between 0 and 1.
It specifies how much the soft grid is used. 0 means turning off
the soft grid; 1 means turning on the soft grid fully.
HARD <float> a float number between 0 and 1;
It specifies how much the hard grid is used. 0 means turning off
the hard grid; 1 means turning on the hard grid fully.
EMAX <float> a positive float number.
MINE <float> a negative float number
MAXE <float> a positive float number
The above three parameters (EMAX, MINE, MAXE) specifies the softness of
nonbonded interactions between atoms. The meaning of these parameters are presented
in the documention ./doc/grid.info.
EPS <float> a positive float number. Distance dependent dielectric (r*eps) is used.
Two grid potentials (soft and hard) with different softness parameters (i.e. EMAX, MINE,
MAXE) are included in the OpenMM system. The command here is for specifying which grid
to use.
Run Simulated Anneling:
OMMD SIAN -
NSTEP <integer> -
FIRST <float> FINAT <float> INCT <float> NHRQ <integer>-
FRIC <float>
NSTEP the number of steps
FIRST the inital temperature for simulated annealing
FINAT the final temperature for simulated annealing
NHRQ the frequcy of changing the temperature
INCT the incremental temperature
Copy Coordinates from OMMD to the Main Coordinates
OMMD COOR IDXC <integer>
IDXC the index of the cope of flexible atoms whose coordinates in the main
set are set using the coordinates from OMMD
Detailed Description of Options in Commands
Read Two Grid Potentials:
OMMD GRID UNIS <integer> UNIH <integer> [Formatted]
UNIS Unit from which to read the soft protein grid potentials
UNIH Unit from which to read the hard protein grid potentials
Formatted Set if the grid potential is in ASCII format
This command reads two grid potentials (soft and hard) for the fixed part of
protein. The grid is generated using grid command (» grid ).
Create OpenMM System and Context:
OMMD BUILD -
[ SELE <fixed atom selection> END ] -
SELE <flexible atom selection> END -
NCOPY <integer>
[nofi] [GRHB]
NCOPY num of copies of flexible atoms
nofi only flexible atoms are used to build the OpenMM system
GRHB The grid energy calculation includes the customizable grids.
Given the fixed atom selection and the flexible atom selection, this command
create an OpenMM system, which comprises of one copy of the fixed atoms and
NCOPY copies of the flexible atoms. When there are no fixed atoms, as
in the case of flexible-ligand and rigid-protein docking, only the flexible atom
selection is specified to be the ligand atoms and nofi option has to be turned on.
When part of the protein is also flexible, the flexible atom selection should include
both ligand atoms and flexible protein atoms and the fixed atom selection should
include the atoms to which the flexible part of the protein connect. During the MD-based
simulated annealing, only the atoms in the flexible atom selection moves. Although
the atoms in the fixed atom selection do not move, they have to be included in the
system such that the flexible part of the protein does not lose bonds with the fixed
part and drift away. This command also creates an OpenMM context with CUDA platform.
Set Positions from Main Coordinates:
OMMD SETC IDXC <integer>
IDXC the index of the copye of flexible atoms whose positions are set based on
the main coordinates.
Change the softness of grid potential:
OMMD CGRS -
SOFT <float> HARD <float> -
EMAX <float> MINE <float> MAXE <float> -
EPS <float>
SOFT <float> a float number between 0 and 1.
It specifies how much the soft grid is used. 0 means turning off
the soft grid; 1 means turning on the soft grid fully.
HARD <float> a float number between 0 and 1;
It specifies how much the hard grid is used. 0 means turning off
the hard grid; 1 means turning on the hard grid fully.
EMAX <float> a positive float number.
MINE <float> a negative float number
MAXE <float> a positive float number
The above three parameters (EMAX, MINE, MAXE) specifies the softness of
nonbonded interactions between atoms. The meaning of these parameters are presented
in the documention ./doc/grid.info.
EPS <float> a positive float number. Distance dependent dielectric (r*eps) is used.
Two grid potentials (soft and hard) with different softness parameters (i.e. EMAX, MINE,
MAXE) are included in the OpenMM system. The command here is for specifying which grid
to use.
Run Simulated Anneling:
OMMD SIAN -
NSTEP <integer> -
FIRST <float> FINAT <float> INCT <float> NHRQ <integer>-
FRIC <float>
NSTEP the number of steps
FIRST the inital temperature for simulated annealing
FINAT the final temperature for simulated annealing
NHRQ the frequcy of changing the temperature
INCT the incremental temperature
Copy Coordinates from OMMD to the Main Coordinates
OMMD COOR IDXC <integer>
IDXC the index of the cope of flexible atoms whose coordinates in the main
set are set using the coordinates from OMMD
Top
!! define the flexible and fixed atom selections
define backbone -
sele (segid prot .and. -
(type n .or. type ca .or. type c .or. type o .or.-
type oct* .or. type ha* .or. type hn .or. type ht*)) end
define flex -
sele ( segid LIGA ) .or. -
(.byres. (((segid LIGA .and. ( .not. hydrogen )) .around. 5) .and. -
( .not. hydrogen))) .and. ( .not. backbone ) end
define fix sele .not. flex end
!! read grid potentials
open unit 30 read unform name "./grid.bin"
OMMD grid UNIT 30
!! create OpenMM system and context
OMMD build sele fix end sele flex end ncopy 10
!! set positions for all copies of flexible atoms with a loop structure
OMMD setc idxc @i
!! run simulated annealing
OMMD SIAN nstep 27000
!! copy positions for each copy back to main coordiantes
OMMD COOR IDXC @i
!! define the flexible and fixed atom selections
define backbone -
sele (segid prot .and. -
(type n .or. type ca .or. type c .or. type o .or.-
type oct* .or. type ha* .or. type hn .or. type ht*)) end
define flex -
sele ( segid LIGA ) .or. -
(.byres. (((segid LIGA .and. ( .not. hydrogen )) .around. 5) .and. -
( .not. hydrogen))) .and. ( .not. backbone ) end
define fix sele .not. flex end
!! read grid potentials
open unit 30 read unform name "./grid.bin"
OMMD grid UNIT 30
!! create OpenMM system and context
OMMD build sele fix end sele flex end ncopy 10
!! set positions for all copies of flexible atoms with a loop structure
OMMD setc idxc @i
!! run simulated annealing
OMMD SIAN nstep 27000
!! copy positions for each copy back to main coordiantes
OMMD COOR IDXC @i
Top
To install CHARMM with the openmm_dock features, give the configure script the
--with-fftdock
command line option in addition to following the instructions for a normal
configure --with-fftdock ...
To install CHARMM with the openmm_dock features, give the configure script the
--with-fftdock
command line option in addition to following the instructions for a normal
configure --with-fftdock ...