tamd (c37b2)
Torsion Angle Molecular Dynamics (TAMD) Module
Purpose: carry out molecular dynamics and energy minimization in torsional
space using atomic forces in Cartesian space. The Newton-Euler Inverse
Mass Operator (NEIMO) recursive algorithm of Jain et al. J. Comput. Phys.
1993, 106, 258-268 was used to solve the equations of motion in internal
coordinates.
WARNING: The module is still being developed and may change in the future.
Please report problems and direct questions and comments to Jianhan Chen
(jianhanc@scripps.edu) or Charles L. Brooks, III (brooks@scripps.edu).
REFERENCES:
A. Jain, N. Vaidehi and K. Kreutz-Delgado, J. Comp. Phys. 1993, 106, 258-268.
C. D. Schwieters and G. M. Clore, J. Magn. Reson. 2001, 152, 288-302.
J. Chen, W. Im and C. L. Brooks, III, J. Comp. Chem. 2005, 26, 1565-1578.
* Syntax | Syntax of the TAMD commands
* Function | Purpose of each of the commands
* Examples | Usage examples of the TAMD analysis commands
Purpose: carry out molecular dynamics and energy minimization in torsional
space using atomic forces in Cartesian space. The Newton-Euler Inverse
Mass Operator (NEIMO) recursive algorithm of Jain et al. J. Comput. Phys.
1993, 106, 258-268 was used to solve the equations of motion in internal
coordinates.
WARNING: The module is still being developed and may change in the future.
Please report problems and direct questions and comments to Jianhan Chen
(jianhanc@scripps.edu) or Charles L. Brooks, III (brooks@scripps.edu).
REFERENCES:
A. Jain, N. Vaidehi and K. Kreutz-Delgado, J. Comp. Phys. 1993, 106, 258-268.
C. D. Schwieters and G. M. Clore, J. Magn. Reson. 2001, 152, 288-302.
J. Chen, W. Im and C. L. Brooks, III, J. Comp. Chem. 2005, 26, 1565-1578.
* Syntax | Syntax of the TAMD commands
* Function | Purpose of each of the commands
* Examples | Usage examples of the TAMD analysis commands
Top
Syntax
[SYNTAX TAMD functions]
Syntax:
TAMD enter the TAMD module
END exit the TAMD module
Subcommands:
RESET reset all TAMD variables.
CLUSter atom-selection
TREE { SETUp [TOPV charmm-topology-version] }
{ CHECk }
{ READ UNIT INTEGER }
{ WRITe UNIT INTEGER }
{ PRINt }
MINI { SD steepd-spec } [ nonbond-spec ] [ hbond-spec ] -
[ INBFrq 0 ] [ IHBFrq 0 ] [NOUPdate] -
[STEP real] [ frequency-spec ] [ tolerence-spec ]
DYNA { STARt } [ dynamics-parameters ] [ Berendsen-thermostat ]
{ STRT }
{ RESTart }
atoms-selection::= a selection of a group of atoms
charmm-topology-version::= { 19 } (param19)
{ 22 } (param22)
hbond-spec::=» hbonds .
nonbond-spec::=» nbonds .
frequency-spec::= [NSTEP int] [IHBFrq int] [INBFrq int] [NPRInt int]
tolerence-spec::= [TOLENR real] [TOLGRD real] [TOLITR int] [TOLSTP real]
» minmiz .
dynamics-parameters::=» dynamc .
Berendsen-thermostat::= [QREF real] [TREF real]
Syntax
[SYNTAX TAMD functions]
Syntax:
TAMD enter the TAMD module
END exit the TAMD module
Subcommands:
RESET reset all TAMD variables.
CLUSter atom-selection
TREE { SETUp [TOPV charmm-topology-version] }
{ CHECk }
{ READ UNIT INTEGER }
{ WRITe UNIT INTEGER }
{ PRINt }
MINI { SD steepd-spec } [ nonbond-spec ] [ hbond-spec ] -
[ INBFrq 0 ] [ IHBFrq 0 ] [NOUPdate] -
[STEP real] [ frequency-spec ] [ tolerence-spec ]
DYNA { STARt } [ dynamics-parameters ] [ Berendsen-thermostat ]
{ STRT }
{ RESTart }
atoms-selection::= a selection of a group of atoms
charmm-topology-version::= { 19 } (param19)
{ 22 } (param22)
hbond-spec::=» hbonds .
nonbond-spec::=» nbonds .
frequency-spec::= [NSTEP int] [IHBFrq int] [INBFrq int] [NPRInt int]
tolerence-spec::= [TOLENR real] [TOLGRD real] [TOLITR int] [TOLSTP real]
» minmiz .
dynamics-parameters::=» dynamc .
Berendsen-thermostat::= [QREF real] [TREF real]
Top
General discussion regarding the TAMD module
1. Tree Topology Setup
-----------------------
The molecule must be represented by a tree topology for energy minimization
or molecular dynamics to be carried out in torsion space. The tree consists
of rigid bodies of atoms with invariable relative positions (clusters)
connected by hinges where the permissible relative motion between adjoined
clusters can be partially constrained. Such a tree topology can be setup
fully automatically for standard CHARMM param19/22 residues or
semi-automatically when the molecule contains non-standard modifications.
The whole process is accomplished by combination of two subcommands: CLUSter
and TREE SETUp.
CLUSter command forces the selected atoms to belong to the same cluster.
It can be applied multiple times such all desired groups can be marked.
TREE SETUp is used to finish the tree topology. If there are no previous marked
clusters (specified by CLUSter commands), the command will groups the atoms
into clusters based on predefined rules and generate the tree data structures.
If there exist previous defined clusters, the command will group the unmarked
atoms into clusters and then generate the tree structure.
Typically a simple TREE SETUp command is sufficient to setup the tree topology.
The other extreme case is to manually cluster all atoms and then use TREE SETUp
to find all the hinges and build the tree.
When the system consists of multiple chains (i.e., not covalently connected),
each chain needs to have different SEGID in order for the TREE SETUp to work.
TREE CHECk checks the self-consistency of tree topology. In addition, PRNLEV
can be set to be 6 or above to prompt TREE SETUp to print out the final tree
topology for inspection.
BOMLEV can be set to be -1 or lower such that the TREE SETUp routine can
proceed to the end regardless of the intermediate errors.
TREE READ and TREE WRITe commands read and write tree files.
TREE PRINt command prints the tree to the standout.
2. Energy Minimization
-----------------------
Energy minimization can be carried out directly in torsion space. The gradient
along internal coordinates can be computed from the Cartesian forces based on
NEIMO algorithm. Currently only Steepest Decent is implemented. Note that
the torsion coordinates are coupled and thus SD minimization (as well as
other more sophisticated minimization algorithms) is less efficient compared to
its counterpart in Cartesian space. Typically only limited minimization is
possible and smaller steps should be used. It is particularly problematic when
harmonic restraints of atomic positions are present.
3. Molecular Dynamics
-----------------------
The accessible time scale of traditional molecular dynamics (MD) simulations in
Cartesian coordinate is severely limited by the femtosecond integration time
steps required by high-frequency bond and angle degrees of freedom. However,
interesting conformational changes of proteins involve mainly torsional degrees
of freedom. Carrying out molecular dynamics directly in torsion space does not
only exclusively sample most relevant degrees of freedom, but also allows
larger integration time steps with elimination of hard degrees of freedom.
Most parameters of DYNA in TAMD are exactly the same as those in a regular
algorithm. Currently TAMD always employs a modified Leap-Frog algorithm and
a simple Berendsen's thermostat. When a negative QREF is given,
constant-energy (NVE) simulation will be carried out instead.
Direct use of a Cartesian force field like CHARMM PARAM22 in TAMD can be
problematic because the rigid covalent geometry introduces severe distortions
of underlying potential surface. CMAP coorection terms in combination with
softcore vdW and electrostatic interactions can be used to effectively restore
the potential surface in torsion space. For PARAM22 force field, such
corrections have been constructed for all standard residues except proline.
These force field modifications can be loaded through special topology and
parameter files. Note that specific bond and angle geometry is required for
these corretions to be meaningful. This is not a problem for folding
simulations from an extended chain build by IC BUILD. However, to initiate
TAMD simulation from a given structure, one needs to "twist" the covalent
geometry to be consistent with the coorrections terms. This can be readily
achieved through quick energy minimization with CONS IC retraints while
turning off other interactions. An example is given in the next section.
Also note that the current topology and parameter files have not been
extensively tested with peptide folding simulations yet and it is almost
certain that addditional adjustment is required for proper balance between
helical and extended (beta) states.
4. Non-TAMD commands parsed
---------------------------
Several essential commands are parsed inside TAMD module. They include CONS,
COOR ENER, GETE, I/O (READ, WRITE, OPEN, CLOSE, TITLES) and miscellaneous
commands.
General discussion regarding the TAMD module
1. Tree Topology Setup
-----------------------
The molecule must be represented by a tree topology for energy minimization
or molecular dynamics to be carried out in torsion space. The tree consists
of rigid bodies of atoms with invariable relative positions (clusters)
connected by hinges where the permissible relative motion between adjoined
clusters can be partially constrained. Such a tree topology can be setup
fully automatically for standard CHARMM param19/22 residues or
semi-automatically when the molecule contains non-standard modifications.
The whole process is accomplished by combination of two subcommands: CLUSter
and TREE SETUp.
CLUSter command forces the selected atoms to belong to the same cluster.
It can be applied multiple times such all desired groups can be marked.
TREE SETUp is used to finish the tree topology. If there are no previous marked
clusters (specified by CLUSter commands), the command will groups the atoms
into clusters based on predefined rules and generate the tree data structures.
If there exist previous defined clusters, the command will group the unmarked
atoms into clusters and then generate the tree structure.
Typically a simple TREE SETUp command is sufficient to setup the tree topology.
The other extreme case is to manually cluster all atoms and then use TREE SETUp
to find all the hinges and build the tree.
When the system consists of multiple chains (i.e., not covalently connected),
each chain needs to have different SEGID in order for the TREE SETUp to work.
TREE CHECk checks the self-consistency of tree topology. In addition, PRNLEV
can be set to be 6 or above to prompt TREE SETUp to print out the final tree
topology for inspection.
BOMLEV can be set to be -1 or lower such that the TREE SETUp routine can
proceed to the end regardless of the intermediate errors.
TREE READ and TREE WRITe commands read and write tree files.
TREE PRINt command prints the tree to the standout.
2. Energy Minimization
-----------------------
Energy minimization can be carried out directly in torsion space. The gradient
along internal coordinates can be computed from the Cartesian forces based on
NEIMO algorithm. Currently only Steepest Decent is implemented. Note that
the torsion coordinates are coupled and thus SD minimization (as well as
other more sophisticated minimization algorithms) is less efficient compared to
its counterpart in Cartesian space. Typically only limited minimization is
possible and smaller steps should be used. It is particularly problematic when
harmonic restraints of atomic positions are present.
3. Molecular Dynamics
-----------------------
The accessible time scale of traditional molecular dynamics (MD) simulations in
Cartesian coordinate is severely limited by the femtosecond integration time
steps required by high-frequency bond and angle degrees of freedom. However,
interesting conformational changes of proteins involve mainly torsional degrees
of freedom. Carrying out molecular dynamics directly in torsion space does not
only exclusively sample most relevant degrees of freedom, but also allows
larger integration time steps with elimination of hard degrees of freedom.
Most parameters of DYNA in TAMD are exactly the same as those in a regular
algorithm. Currently TAMD always employs a modified Leap-Frog algorithm and
a simple Berendsen's thermostat. When a negative QREF is given,
constant-energy (NVE) simulation will be carried out instead.
Direct use of a Cartesian force field like CHARMM PARAM22 in TAMD can be
problematic because the rigid covalent geometry introduces severe distortions
of underlying potential surface. CMAP coorection terms in combination with
softcore vdW and electrostatic interactions can be used to effectively restore
the potential surface in torsion space. For PARAM22 force field, such
corrections have been constructed for all standard residues except proline.
These force field modifications can be loaded through special topology and
parameter files. Note that specific bond and angle geometry is required for
these corretions to be meaningful. This is not a problem for folding
simulations from an extended chain build by IC BUILD. However, to initiate
TAMD simulation from a given structure, one needs to "twist" the covalent
geometry to be consistent with the coorrections terms. This can be readily
achieved through quick energy minimization with CONS IC retraints while
turning off other interactions. An example is given in the next section.
Also note that the current topology and parameter files have not been
extensively tested with peptide folding simulations yet and it is almost
certain that addditional adjustment is required for proper balance between
helical and extended (beta) states.
4. Non-TAMD commands parsed
---------------------------
Several essential commands are parsed inside TAMD module. They include CONS,
COOR ENER, GETE, I/O (READ, WRITE, OPEN, CLOSE, TITLES) and miscellaneous
commands.
Top
Examples
Example (1) : setup tree, do minimization and dynamics for a peptide with
----------- standard CHARMM param19/22 residues.
open read card unit 10 name @toppar/top_all22_prot.inp
read rtf card unit 10
open read card unit 10 name @toppar/par_all22_prot.inp
read para card unit 10
close unit 10
open read unit 10 card name @pdbfile
read sequence pdb unit 10
generate @segid setup
open read card unit 10 name @pdbfile
coor read pdb unit 10 resid
close unit 10
ic param
ic build
hbuild
coor copy comp
NBOND atom switch cdie vdw vswitch bycb -
ctonnb 16.0 ctofnb 20.0 cutnb 24.0
! enter TAMD modulde
TAMD
reset
! setup the tree topology automatically
tree setup
! check the self-consistency of the tree toplogy
tree check
! write out the tree (not really necessary, but why not?)
open write unit 10 card name tree.dat
tree write unit 10
* this is a tamd tree file
*
! some quick minimization (remember that minimization in torsion space is
! less efficient due to the non-canonical coordinates)
mini sd nstep 200 step 0.01 nprint 20 maxt 0.1 tole 0.0001
! a short constant-temperature MD
open write unit 30 card name tamd.rest
open write unit 31 file name tamd.dcd
dyna start iseed 231234 echeck 2000 -
nstep 5000 timestep 0.005 qref 20 tref 300 first 0 -
nsavc 100 nprint 200 iprfrq 100000 nsavv 0 isvfrq -1 -
iunrea -29 iunwri 30 iuncrd 31 iunvel -1 -
ntrfrq 2000 iasors 1
! compute heavy atom rmsd from initial structure (the comparision cooridinates
! are not overwritten during TAMD)
coor orient rms select .not. hydrogen end
! write out the final pdb
open write unit 10 card name tamd.pdb
coor write pdb unit 10
* after a short tamd, heavy atom rmsd is now: ?rms
*
END
Example (2): setup a tree topology semi-automatically for a polymer chain
----------- with non-standard residues (a modified alanine dipeptide)
....
read sequence ala 1
generate PEPT first ACE last CT3 setup
ic param
ic seed 1 N 1 CA 1 C
ic build
bomlev -1
delete atom select type CAY .or. type HY# .or. type CAT .or. type HT# end
bomlev 0
TAMD
reset
cluster select type cy .or. type oy .or. type n .or. type hn -
.or. type ca .or. type ha .or. type c .or. type o -
.or. type nt .or. type hnt end
bomlev -1
wrnlev 0
prnlev 6
tree setup topv 22
prnlev 5
wrnlev 5
bomlev 0
tree check
END
....
Example (3): enforce the covalent geometry to be consistent those defined in
------------ the topology file (IC tables).
!===========================================================================
! read in the TAMD ICFF top/par files (ahbb4)
set toppar = toppar/tamdfff
open read card unit 10 name @toppar/top_all22_prot_cmap.ahbb4.inp
read rtf card unit 10
open read card unit 10 name @toppar/par_all22_prot_tadcmap.ahbb4.inp
read para card unit 10
! addition CMAP terms for chi1 coorrection maps
open read card unit 10 name @toppar/par_tadmap.chi1.ahbb4..inp
read para card unit 10 append
close unit 10
!(set up PSF and read in the coordinates)
....
! using CONS IC to enforce the covalent geometry
if @?force eq 0 set force = 1000.0
cons ic bond @force angle @force impr @force diheral 0.0
! weak harmonic restaints to prevent large adjustments
cons harm force 1.0 select .not. hydrogen end
! constraint the peptide plane omega dihedral (CA-C-N-CA)
! OMEGA should be consistent with the value in topology file
define any selet bynu 1 end
set inx = ?selresi
calc end = ?selresi + ?nres - 1
calc next = @inx + 1
label nextresi
define any select resid @inx end
if ?selresn eq PRO goto skipcdihe
define any select resid @next end
if ?selresn eq PRO goto skipcdihe
cons dihe force 4000 min @OMEGA width 0.0 -
PRO0 @inx CA PRO0 @inx C PRO0 @next N PRO0 @next CA
label skipcdihe
incr inx by 1
incr next by 1
if next le @end goto nextresi
! turn off unnecessary energy terms.
skip all excl cic harm cdihe
ic save
! quick minimization to enforce covalent geometry (bonds, angles and impropers)
mini sd nstep 100 nprint 50 step 0.005
mini abnr nstep 100 nprint 50 step 0.005
! cleanup the restaints and other setups
skip none
cons harm clear
cons cldh
cons ic bond 0.0 angle 0.0 impr 0.0 diheral 0.0
! verify that the structure is now consistent with the topology IC tables
ic scale bond -1.0 angle -1.0 dihe -1.0
ic fill append
ic print !unit 12
!==========================================================================
Examples
Example (1) : setup tree, do minimization and dynamics for a peptide with
----------- standard CHARMM param19/22 residues.
open read card unit 10 name @toppar/top_all22_prot.inp
read rtf card unit 10
open read card unit 10 name @toppar/par_all22_prot.inp
read para card unit 10
close unit 10
open read unit 10 card name @pdbfile
read sequence pdb unit 10
generate @segid setup
open read card unit 10 name @pdbfile
coor read pdb unit 10 resid
close unit 10
ic param
ic build
hbuild
coor copy comp
NBOND atom switch cdie vdw vswitch bycb -
ctonnb 16.0 ctofnb 20.0 cutnb 24.0
! enter TAMD modulde
TAMD
reset
! setup the tree topology automatically
tree setup
! check the self-consistency of the tree toplogy
tree check
! write out the tree (not really necessary, but why not?)
open write unit 10 card name tree.dat
tree write unit 10
* this is a tamd tree file
*
! some quick minimization (remember that minimization in torsion space is
! less efficient due to the non-canonical coordinates)
mini sd nstep 200 step 0.01 nprint 20 maxt 0.1 tole 0.0001
! a short constant-temperature MD
open write unit 30 card name tamd.rest
open write unit 31 file name tamd.dcd
dyna start iseed 231234 echeck 2000 -
nstep 5000 timestep 0.005 qref 20 tref 300 first 0 -
nsavc 100 nprint 200 iprfrq 100000 nsavv 0 isvfrq -1 -
iunrea -29 iunwri 30 iuncrd 31 iunvel -1 -
ntrfrq 2000 iasors 1
! compute heavy atom rmsd from initial structure (the comparision cooridinates
! are not overwritten during TAMD)
coor orient rms select .not. hydrogen end
! write out the final pdb
open write unit 10 card name tamd.pdb
coor write pdb unit 10
* after a short tamd, heavy atom rmsd is now: ?rms
*
END
Example (2): setup a tree topology semi-automatically for a polymer chain
----------- with non-standard residues (a modified alanine dipeptide)
....
read sequence ala 1
generate PEPT first ACE last CT3 setup
ic param
ic seed 1 N 1 CA 1 C
ic build
bomlev -1
delete atom select type CAY .or. type HY# .or. type CAT .or. type HT# end
bomlev 0
TAMD
reset
cluster select type cy .or. type oy .or. type n .or. type hn -
.or. type ca .or. type ha .or. type c .or. type o -
.or. type nt .or. type hnt end
bomlev -1
wrnlev 0
prnlev 6
tree setup topv 22
prnlev 5
wrnlev 5
bomlev 0
tree check
END
....
Example (3): enforce the covalent geometry to be consistent those defined in
------------ the topology file (IC tables).
!===========================================================================
! read in the TAMD ICFF top/par files (ahbb4)
set toppar = toppar/tamdfff
open read card unit 10 name @toppar/top_all22_prot_cmap.ahbb4.inp
read rtf card unit 10
open read card unit 10 name @toppar/par_all22_prot_tadcmap.ahbb4.inp
read para card unit 10
! addition CMAP terms for chi1 coorrection maps
open read card unit 10 name @toppar/par_tadmap.chi1.ahbb4..inp
read para card unit 10 append
close unit 10
!(set up PSF and read in the coordinates)
....
! using CONS IC to enforce the covalent geometry
if @?force eq 0 set force = 1000.0
cons ic bond @force angle @force impr @force diheral 0.0
! weak harmonic restaints to prevent large adjustments
cons harm force 1.0 select .not. hydrogen end
! constraint the peptide plane omega dihedral (CA-C-N-CA)
! OMEGA should be consistent with the value in topology file
define any selet bynu 1 end
set inx = ?selresi
calc end = ?selresi + ?nres - 1
calc next = @inx + 1
label nextresi
define any select resid @inx end
if ?selresn eq PRO goto skipcdihe
define any select resid @next end
if ?selresn eq PRO goto skipcdihe
cons dihe force 4000 min @OMEGA width 0.0 -
PRO0 @inx CA PRO0 @inx C PRO0 @next N PRO0 @next CA
label skipcdihe
incr inx by 1
incr next by 1
if next le @end goto nextresi
! turn off unnecessary energy terms.
skip all excl cic harm cdihe
ic save
! quick minimization to enforce covalent geometry (bonds, angles and impropers)
mini sd nstep 100 nprint 50 step 0.005
mini abnr nstep 100 nprint 50 step 0.005
! cleanup the restaints and other setups
skip none
cons harm clear
cons cldh
cons ic bond 0.0 angle 0.0 impr 0.0 diheral 0.0
! verify that the structure is now consistent with the topology IC tables
ic scale bond -1.0 angle -1.0 dihe -1.0
ic fill append
ic print !unit 12
!==========================================================================