# hqbm (c45b2)

The HQBM Module of CHARMM

By Emanuele Paci, 1997/2000

HQBM is an external perturbation designed induce conformational

changes in macromolecules. The time dependent perturbation is designed

to introduce a very small perturbation to the short time dynamics of

the system and does not affect the conservation of the constants of

motion of the system (the conservation of the total energy or of the

suitable conserved quantity when an extended Lagrangian is used can

then be used as a check of the correctness of the forces).

The external perturbation needs:

- a reference (or target) structure

- a reaction coordinate which defines a "distance" from the

reference structure

* Syntax | Syntax of the HQBM command

* Function | Purpose of each of the keywords

* Input | HQBM Input Description

By Emanuele Paci, 1997/2000

HQBM is an external perturbation designed induce conformational

changes in macromolecules. The time dependent perturbation is designed

to introduce a very small perturbation to the short time dynamics of

the system and does not affect the conservation of the constants of

motion of the system (the conservation of the total energy or of the

suitable conserved quantity when an extended Lagrangian is used can

then be used as a check of the correctness of the forces).

The external perturbation needs:

- a reference (or target) structure

- a reaction coordinate which defines a "distance" from the

reference structure

* Syntax | Syntax of the HQBM command

* Function | Purpose of each of the keywords

* Input | HQBM Input Description

Top

[INPUT HQBM command]

- read the reference structure

OPEN UNIT 1 READ FORMATTED NAME coor0.crd

READ COOR CARD COMP UNIT 1

CLOSE UNIT 1

- call the perturbation choosing a coupling constant [ALPHA], a

reaction coordinate (see summary below), and a selection of atoms

which define the reaction coordinate. Several biases may be

in operation in any time: each must be set up by a separate

HQBM command. The general form of the setup command is:

HQBM [RC1 | RC2 | RC3...] ALPHA real [IUNJ integer] [XIMAX real] -

[ANAL FIRSTU integer NUNIT integer] -

coord-specific-options

coord-specific-options are listed below for each coordinate

- energy NO LONGER NEEDS TO BE CALLED after HQBM !!

this won't affect anything, just increase the step number by 1 each time.

necessary in order to have multiple reaction coordinates & keep the

output synchronous.

- reset all HQBM biases, i.e. EHQBM = 0.0 always

HQBM RESET

- only change the coupling constant (ALPHA); useful for equilibration

HQBM RCX UPALPHA real

RCX is RC1, RC2, etc. - which ever reaction coordinate needs

alpha updated

'real' is a new value for the coupling constant.

- coord-specific-options:

A description of each coordinate, and the options is given in the

section Function. Also, this will surely be out of date rapidly,

so the source is the best recourse.

RC1: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [READLIST integer] -

[READREF integer] [IUNK integer] atom-selection

RC2: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [READLIST integer] -

[IUNK integer] atom-selection

RC3/PHI: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [COMB] [AVEP AALPHA real] -

[READLIST integer] [IUNR real] [BETA real] [EXCL real] -

[RCUT real] [TOL real] [ZERO] [IUND integer] -

IUNP real atom-selection

RC4/HX: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [IUNK integer] [IUND integer] -

[EEF1] [NHCON] [SPLIT] [NONN [CUTON real] [CUTOF real]] [BETA real] -

[BETC real] [BETH real] [EXCL real] [RCUT real] [HCUT real] [ZERO] -

IUNP integer -

atom-selection1 atom-selection2 atom-selection3 atom-selection4

RC5: [NOEN] [TARGET real] [READLIST integer] atom-selection

RC6/NOE: [AWAY] [SMD GAMMA real] [FIX] [ZERO] [SIXT | LINE] [NOEN] -

[IUND integer] IUNN integer

RC7/RDC: ... not done yet ...

RC8/S2 ***: [IUND integer] [FIX] IUNS integer

RC9/J3: [IUND integer] [IUNK integer] [ZERO] [NOEN] J3UNIT integer

RC10/PSI ***: [IUND integer] [IUNK integer] [FIX] [ZERO] [BETA real]

[RCUT real] [TOL real] IUNP integer

*** These coordinates can ONLY be used in the replica/ensemble version.

[INPUT HQBM command]

- read the reference structure

OPEN UNIT 1 READ FORMATTED NAME coor0.crd

READ COOR CARD COMP UNIT 1

CLOSE UNIT 1

- call the perturbation choosing a coupling constant [ALPHA], a

reaction coordinate (see summary below), and a selection of atoms

which define the reaction coordinate. Several biases may be

in operation in any time: each must be set up by a separate

HQBM command. The general form of the setup command is:

HQBM [RC1 | RC2 | RC3...] ALPHA real [IUNJ integer] [XIMAX real] -

[ANAL FIRSTU integer NUNIT integer] -

coord-specific-options

coord-specific-options are listed below for each coordinate

- energy NO LONGER NEEDS TO BE CALLED after HQBM !!

this won't affect anything, just increase the step number by 1 each time.

necessary in order to have multiple reaction coordinates & keep the

output synchronous.

- reset all HQBM biases, i.e. EHQBM = 0.0 always

HQBM RESET

- only change the coupling constant (ALPHA); useful for equilibration

HQBM RCX UPALPHA real

RCX is RC1, RC2, etc. - which ever reaction coordinate needs

alpha updated

'real' is a new value for the coupling constant.

- coord-specific-options:

A description of each coordinate, and the options is given in the

section Function. Also, this will surely be out of date rapidly,

so the source is the best recourse.

RC1: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [READLIST integer] -

[READREF integer] [IUNK integer] atom-selection

RC2: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [READLIST integer] -

[IUNK integer] atom-selection

RC3/PHI: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [COMB] [AVEP AALPHA real] -

[READLIST integer] [IUNR real] [BETA real] [EXCL real] -

[RCUT real] [TOL real] [ZERO] [IUND integer] -

IUNP real atom-selection

RC4/HX: [AWAY] [SMD GAMMA real] [FIX] [NOEN] [IUNK integer] [IUND integer] -

[EEF1] [NHCON] [SPLIT] [NONN [CUTON real] [CUTOF real]] [BETA real] -

[BETC real] [BETH real] [EXCL real] [RCUT real] [HCUT real] [ZERO] -

IUNP integer -

atom-selection1 atom-selection2 atom-selection3 atom-selection4

RC5: [NOEN] [TARGET real] [READLIST integer] atom-selection

RC6/NOE: [AWAY] [SMD GAMMA real] [FIX] [ZERO] [SIXT | LINE] [NOEN] -

[IUND integer] IUNN integer

RC7/RDC: ... not done yet ...

RC8/S2 ***: [IUND integer] [FIX] IUNS integer

RC9/J3: [IUND integer] [IUNK integer] [ZERO] [NOEN] J3UNIT integer

RC10/PSI ***: [IUND integer] [IUNK integer] [FIX] [ZERO] [BETA real]

[RCUT real] [TOL real] IUNP integer

*** These coordinates can ONLY be used in the replica/ensemble version.

Top

The following section describes the keywords of the HQBM command.

HQBM introduces a half quadratic perturbation on a given reaction

coordinate (see below)

Meaning of the HQBM parameters

==============================

General Parameters & Parameters common to many coordinates

-----------------------------------------------------------

(check syntax to see whether a given option is supported with the reaction

coordinate of interest)

# AWAY drive the system away from the reference coordinate.

As an example, if the reaction coordinate measures the deviation from

a reference conformation, the perturbation will increase it.

# ALPHA is the force constant of the half harmonic potential.

# RC1, RC2, RC3/PHI, RC4/HX, RC5, RC6/NOE, RC7/RDC, RC8/S2, RC9/J3, RC10/PSI

will select other reaction coordinates (descriptions below)

# atom-selection: some coordinates require an atom selection -

only the selected atoms will be used to define the coordinate.

See below for more specific definitions.

# IUNJ: write the output (istep rc(t) max(rc)) on unit IUNJ

# FIX: make the target value of the reaction coordinate the initial value.

# ZERO: make the target value of the reaction coordinate ZERO (same as FXRG).

# IUND integer: a unit to dump calculated phi-values, protection factors to

at regular intervals during the trajectory

# IUNK integer: a unit to dump initial contact lists to.

# SMD: use schulten style "steered molecular dynamics". This requires

a speed to move the target reaction coordinate, given by the

GAMMA option.

# NOEN: when using the ensemble version of the code (see: ensemble.info)

this will force a particular reaction coordinate NOT to use

the ensemble averaged form.

# BETA real: the value of beta in the smooth function for counting native

contacts 1.0/(1+exp(beta(r-rcut))).

# RCUT real: see entry for BETA above.

# TOL real: When counting native contacts in non-native structures, allow

an extra TOL angstroms (i.e. rcut is increased by TOL).

# EXCL integer: Do not count contacts between residues separated by fewer

than EXCL.

Description of each coordinate and its specific parameters

----------------------------------------------------------

RC1: A reaction coordinate based on the mean square difference from the

target coordinates. If the target coords are all set to zero

(e.g. with SCALAR), the reaction coordinate is like a radius

of gyration (it is in fact the square of the radius of gyration

over the selected atoms assuming equal masses). If only two atoms

are selected, the reaction coordinate is the distance between them.

[READLIST integer] read a list of atom index pairs specifying native

contacts, i.e. in the format:

i1 j1

i2 j2

...

[READREF integer] read a list of atom index pairs specifying native

contacts, AND distances between them, i.e.:

i1 j1 r1

i2 j2 r2

...

RC2: Works exactly like RC1, except that instead of rho = \sum_ij (r_{ij}-r_{ij}^{ref})^2,

rho = sum_{ij} exp(((r_{ij}-r_{ij}^{ref})/r_{ij}^{ref})^2).

RC3/PHI: Drive system to satisfy experimental phi-values, defined as a residue-based

fraction of native contacts.

[COMB] : if specified, the native contact list will be constructed

by making all possible combinations of the atom selection.

Used for hydrophobic clustering in unfolded state (Julia Wirmer).

[AVEP AALPHA real] : ONLY works with ensemble code. As an ensemble,

the replicas are driven to satisfy the expt phi-values; the

AVEP bias ensures that each replica will also satisfy the

average phi value, AALPHA being a separate coupling constant

for this. Only one HQBM invokation is needed for both the

standard phi and the average phi (by default average phi is off).

[READLIST integer] : read native contacts from a file:

i1 j1

i2 j2

...

[IUNR real] ????

[IUNP real]: unit with phi-values:

res1 phi1

res2 phi2

...

atom-selection: the atoms to use for counting native contacts if

not reading native contact list from a file.

RC4/HX: Hydrogen exchange bias. System driven to satisfy experimental

protection factors. Protection factors defined as logP = Bc*Nc+Bh*Nh

atom-selection1: defines heavy atom contacts

atom-selection2: oxygen selection (for hbonds)

atom-selection3: nitrogen selection (only for EEF1 - otherwise ignored)

atom-selection4: hydrogen selection (for hbonds)

[EEF1] - this ONLY works in analysis mode. The EEF1 energy of nitrogen

atom is used for the burial term (Nc). Uses third atom selection.

[NHCON] - used HN_i --- heavy atom contacts for burial

default is heavy_atoms_i --- other heavy atoms

[SPLIT] - when writing to IUND file, separate hydrogen bonding and

burial contributions to the protection factor.

[NONN [CUTON real] [CUTOF real]] - Use all contacts, not just native

ones, for burial. Requires a cutoff function for efficiency.

cutof must be larger than cuton.

[BETC real] = bc above

[BETH real] = bh above

[HCUT real] - cutoff for counting hydrogen bonds (default = 2.4 Angstrom

O-H distance)

[IUNP integer] - unit with protection factors:

res1 logP1 type1

res2 logP2 type2

....

The protection factor "type" is one of 0, -1, or 1:

0: protection factor must be satisfied exactly

-1: protection factor must be smaller than value given

(for residues exchanged in dead time)

1: protection factor must be larger than value given

(for global exchange data)

RC5: Works like RC1, except drives system towards target value specified by TARGET

and holds it there.

RC6/NOE: Drives system towards experimental NOE values.

[SIXT | LINE] - type of averaging. Default is <r^{-3}>^{-1/3}

SIXTh specifies <r^{-6}>^{-1/6}

LINEar is normal (linear) averaging

IUNN integer - unit with noe's, format:

N

i1 j1 lbound1 ubound1

i2 j2 lbound2 ubound2

...

iN jN lboundN uboundN

RC7/RDC: not implemented

RC8/S2: Order parameter bias. Drives an ensemble of configurations

to satisfy experimental order parameters. Obviously, this

ONLY works for the ENSEMBLE code (» ensemble ).

IUNS integer - unit with order parameters, format:

N

i1 j1 S2_1

i2 j2 S2_2

...

iN jN S2_N

RC9/J3: Drive system to satisfy scalar coupling restraints

J3UNIT integer - unit with couplings, format:

i1 j1 k1 l1 A1 B1 C1 D1 J1

i2 j2 k2 l2 A2 B2 C2 D2 J2

...

where i,j,k,l are the atom indices defining

the dihedral, and A, B, C and D are the

karplus parameters using the form of the equation:

J(phi) = A*cos^2(phi+D) + B*cos(phi+D) + C

Ref: Chou et al. JACS, 125, 8959-8966 (2003)

RC10/PSI: Drive system to satisfy psi-values (sosnick papers)

not finished...

The method is described in

E. Paci and M. Karplus. Forced unfolding of fibronectin type 3

modules: An analysis by biased molecular dynamics simulations.

J. Mol. Biol., 288: 441-459, 1999.

TESTCASES (in test/c32test):

============================

hqbm_single_test.inp: This is a test of the single copy versions of

RC1, RC2, RC3, RC4, RC6 & RC9

It may be run in the test directory by invoking:

./test.com arch output bench 32

which will run this + all the other c32 testcases

hqbm_rc3_ens_test.inp: Ensemble test of RC3/PHI -- see below for how to run

hqbm_rc4_ens_test.inp: Ensemble test of RC4/HX -- see below for how to run

hqbm_rc8_ens.inp: Test of RC8 (only ensemble) -- see below for how to run

To run ensemble tests, use the following command in the test directory:

./test.com E arch

in this case the optional fourth command specifying target will be ignored.

The following section describes the keywords of the HQBM command.

HQBM introduces a half quadratic perturbation on a given reaction

coordinate (see below)

Meaning of the HQBM parameters

==============================

General Parameters & Parameters common to many coordinates

-----------------------------------------------------------

(check syntax to see whether a given option is supported with the reaction

coordinate of interest)

# AWAY drive the system away from the reference coordinate.

As an example, if the reaction coordinate measures the deviation from

a reference conformation, the perturbation will increase it.

# ALPHA is the force constant of the half harmonic potential.

# RC1, RC2, RC3/PHI, RC4/HX, RC5, RC6/NOE, RC7/RDC, RC8/S2, RC9/J3, RC10/PSI

will select other reaction coordinates (descriptions below)

# atom-selection: some coordinates require an atom selection -

only the selected atoms will be used to define the coordinate.

See below for more specific definitions.

# IUNJ: write the output (istep rc(t) max(rc)) on unit IUNJ

# FIX: make the target value of the reaction coordinate the initial value.

# ZERO: make the target value of the reaction coordinate ZERO (same as FXRG).

# IUND integer: a unit to dump calculated phi-values, protection factors to

at regular intervals during the trajectory

# IUNK integer: a unit to dump initial contact lists to.

# SMD: use schulten style "steered molecular dynamics". This requires

a speed to move the target reaction coordinate, given by the

GAMMA option.

# NOEN: when using the ensemble version of the code (see: ensemble.info)

this will force a particular reaction coordinate NOT to use

the ensemble averaged form.

# BETA real: the value of beta in the smooth function for counting native

contacts 1.0/(1+exp(beta(r-rcut))).

# RCUT real: see entry for BETA above.

# TOL real: When counting native contacts in non-native structures, allow

an extra TOL angstroms (i.e. rcut is increased by TOL).

# EXCL integer: Do not count contacts between residues separated by fewer

than EXCL.

Description of each coordinate and its specific parameters

----------------------------------------------------------

RC1: A reaction coordinate based on the mean square difference from the

target coordinates. If the target coords are all set to zero

(e.g. with SCALAR), the reaction coordinate is like a radius

of gyration (it is in fact the square of the radius of gyration

over the selected atoms assuming equal masses). If only two atoms

are selected, the reaction coordinate is the distance between them.

[READLIST integer] read a list of atom index pairs specifying native

contacts, i.e. in the format:

i1 j1

i2 j2

...

[READREF integer] read a list of atom index pairs specifying native

contacts, AND distances between them, i.e.:

i1 j1 r1

i2 j2 r2

...

RC2: Works exactly like RC1, except that instead of rho = \sum_ij (r_{ij}-r_{ij}^{ref})^2,

rho = sum_{ij} exp(((r_{ij}-r_{ij}^{ref})/r_{ij}^{ref})^2).

RC3/PHI: Drive system to satisfy experimental phi-values, defined as a residue-based

fraction of native contacts.

[COMB] : if specified, the native contact list will be constructed

by making all possible combinations of the atom selection.

Used for hydrophobic clustering in unfolded state (Julia Wirmer).

[AVEP AALPHA real] : ONLY works with ensemble code. As an ensemble,

the replicas are driven to satisfy the expt phi-values; the

AVEP bias ensures that each replica will also satisfy the

average phi value, AALPHA being a separate coupling constant

for this. Only one HQBM invokation is needed for both the

standard phi and the average phi (by default average phi is off).

[READLIST integer] : read native contacts from a file:

i1 j1

i2 j2

...

[IUNR real] ????

[IUNP real]: unit with phi-values:

res1 phi1

res2 phi2

...

atom-selection: the atoms to use for counting native contacts if

not reading native contact list from a file.

RC4/HX: Hydrogen exchange bias. System driven to satisfy experimental

protection factors. Protection factors defined as logP = Bc*Nc+Bh*Nh

atom-selection1: defines heavy atom contacts

atom-selection2: oxygen selection (for hbonds)

atom-selection3: nitrogen selection (only for EEF1 - otherwise ignored)

atom-selection4: hydrogen selection (for hbonds)

[EEF1] - this ONLY works in analysis mode. The EEF1 energy of nitrogen

atom is used for the burial term (Nc). Uses third atom selection.

[NHCON] - used HN_i --- heavy atom contacts for burial

default is heavy_atoms_i --- other heavy atoms

[SPLIT] - when writing to IUND file, separate hydrogen bonding and

burial contributions to the protection factor.

[NONN [CUTON real] [CUTOF real]] - Use all contacts, not just native

ones, for burial. Requires a cutoff function for efficiency.

cutof must be larger than cuton.

[BETC real] = bc above

[BETH real] = bh above

[HCUT real] - cutoff for counting hydrogen bonds (default = 2.4 Angstrom

O-H distance)

[IUNP integer] - unit with protection factors:

res1 logP1 type1

res2 logP2 type2

....

The protection factor "type" is one of 0, -1, or 1:

0: protection factor must be satisfied exactly

-1: protection factor must be smaller than value given

(for residues exchanged in dead time)

1: protection factor must be larger than value given

(for global exchange data)

RC5: Works like RC1, except drives system towards target value specified by TARGET

and holds it there.

RC6/NOE: Drives system towards experimental NOE values.

[SIXT | LINE] - type of averaging. Default is <r^{-3}>^{-1/3}

SIXTh specifies <r^{-6}>^{-1/6}

LINEar is normal (linear) averaging

IUNN integer - unit with noe's, format:

N

i1 j1 lbound1 ubound1

i2 j2 lbound2 ubound2

...

iN jN lboundN uboundN

RC7/RDC: not implemented

RC8/S2: Order parameter bias. Drives an ensemble of configurations

to satisfy experimental order parameters. Obviously, this

ONLY works for the ENSEMBLE code (» ensemble ).

IUNS integer - unit with order parameters, format:

N

i1 j1 S2_1

i2 j2 S2_2

...

iN jN S2_N

RC9/J3: Drive system to satisfy scalar coupling restraints

J3UNIT integer - unit with couplings, format:

i1 j1 k1 l1 A1 B1 C1 D1 J1

i2 j2 k2 l2 A2 B2 C2 D2 J2

...

where i,j,k,l are the atom indices defining

the dihedral, and A, B, C and D are the

karplus parameters using the form of the equation:

J(phi) = A*cos^2(phi+D) + B*cos(phi+D) + C

Ref: Chou et al. JACS, 125, 8959-8966 (2003)

RC10/PSI: Drive system to satisfy psi-values (sosnick papers)

not finished...

The method is described in

E. Paci and M. Karplus. Forced unfolding of fibronectin type 3

modules: An analysis by biased molecular dynamics simulations.

J. Mol. Biol., 288: 441-459, 1999.

TESTCASES (in test/c32test):

============================

hqbm_single_test.inp: This is a test of the single copy versions of

RC1, RC2, RC3, RC4, RC6 & RC9

It may be run in the test directory by invoking:

./test.com arch output bench 32

which will run this + all the other c32 testcases

hqbm_rc3_ens_test.inp: Ensemble test of RC3/PHI -- see below for how to run

hqbm_rc4_ens_test.inp: Ensemble test of RC4/HX -- see below for how to run

hqbm_rc8_ens.inp: Test of RC8 (only ensemble) -- see below for how to run

To run ensemble tests, use the following command in the test directory:

./test.com E arch

in this case the optional fourth command specifying target will be ignored.