MAKE_RESTRAINTS -- make restraints

RESTRAINT_TYPE = <string:1>	'STEREO'	restraint type to be calculated: 'STEREO' | 'BOND' | 'ANGLE' | 'IMPROPER' | 'DIHEDRAL' | 'MRFP_STEREO' | 'MRFP_BOND' | 'MRFP_ANGLE' | 'MRFP_DIHEDRAL' | 'SPHERE' | 'SPHERE14' | 'LJ' | 'LJ14' | 'COULOMB' | 'COULOMB14' | 'ALPHA' | 'STRAND' | 'SHEET' | 'DISTANCE' | 'USER_DISTANCE' | 'NONB_PAIR_SPLINE' | 'PHI-PSI_BINORMAL' | 'PHI-PSI_CLASS' | 'PHI_DIHEDRAL' | 'PSI_DIHEDRAL' | 'OMEGA_DIHEDRAL' | 'CHI1_DIHEDRAL' | 'CHI2_DIHEDRAL' | 'CHI3_DIHEDRAL' | 'CHI4_DIHEDRAL'
RADII_FACTOR = <real:1>	0.82	factor for van der Waals radii
TOPOLOGY_MODEL = <integer:1>	3	selects topology library: 1-10
DIH_LIB_ONLY = <logical:1>	off	whether to use only library, not homologs for dihedral angle rsrs
MNCH_LIB = <integer:1>	1	which MNCH lib to use in MAKE_RESTRAINTS
INTERSEGMENT = <logical:1>	on	whether to restrain inter-segment non-bonded pairs
ADD_RESTRAINTS = <logical:1>	off	whether to add new restraints to existing restraints
RESIDUE_GROUPING = <integer:1>	1
MAXIMAL_DISTANCE = <real:1>	999	maximal distance for distance restraints
RESIDUE_SPAN_RANGE = <integer:2>	0 99999	range of residues spanning the allowed distances; for MAKE_RESTRAINTS, PICK_RESTRAINTS, non-bonded dynamic pairs
RESIDUE_SPAN_SIGN = <logical:1>	on	whether to do N*(N-1)/2 loop for atom pairs in MAKE_RESTRAINTS RESTRAINT_TYPE = 'distance'
RESTRAINT_SEL_ATOMS = <integer:1>	1	a restraint other than non-bonded pair has to have at least as many selected atoms
NONBONDED_SEL_ATOMS = <integer:1>	1	a non-bonded pair has to have at least as many selected atoms
EXCL_LOCAL = <logical:4>	on on on on	whether to exclude bonds, angles, dihedrals, explicit excl pairs from the homology-derived distance rsrs
ACCESSIBILITY_TYPE = <integer:1>	8	type of solvent accessibility: 1-10
DISTANCE_RSR_MODEL = <integer:1>	1	the model for calculating distance restraints: 1-7
RESTRAINT_STDEV = <real:2>	0.0 1.0	transforming factors for standard deviations (y=a+bx) in models 1-6 or standard deviation for model 7 (a)
RESTRAINT_STDEV2 = <real:3>	0 0 0	transforming standard deviation in models 3-6: S' = S + [ a + b max(0, c-g) ]
RESTRAINT_PARAMETERS = <real:0>	3 1 3 3 4 2 0 0.0 0.087	restraint parameters for 'USER_DISTANCE'
ATOM_FILES_DIRECTORY = <string:1>	'./'	input atom files directory list (e.g., 'dir1:dir2:dir3:./:/')
BASIS_PDF_WEIGHT = <string:1>	'LOCAL'	a method for calculation of basis pdf weights: 'LOCAL' | 'GLOBAL'
BASIS_RELATIVE_WEIGHT = <real:1>	0.05	the cutoff weight of basis pdf's for their removal
RESIDUE_IDS = <string:0>	''	residue id (number:chnid)
SPLINE_ON_SITE = <logical:1>	off	whether to convert restraints to splines
SHEET_H-BONDS = <integer:1>	7	specify hydrogen bonds in a beta-sheet

Requirements:

topology & parameters [& alignment] [& picked atoms sets 2 and 3]

Description:

This command calculates and selects new restraints of a specified type. See the original papers for the most detailed definition and description of the restraints [Šali & Blundell, 1993,Šali & Overington, 1994]. The calculation of restraints of all types is now (partly) limited to the selected atoms only (either set 1, or 2 and 3; see below).

If ADD_RESTRAINTS is off, all old restraints are deleted, otherwise new restraints are added to the old ones.

RESTRAINT_TYPE selects the types of the generated restraints. Only one restraint type can be selected at a time, except for the stereochemical restraints (BOND, ANGLE, DIHEDRAL, IMPROPER) that can all be calculated at the same time. It is useful to distinguish between the stereochemical restraints and homology-derived restraints. The stereochemical restraints are obtained from libraries that depend on atom and/or residue types only (e.g., CHARMM 22 force field [MacKerell et al., 1998] or statistical potentials), and do not require an alignment with template structures. In contrast, the homology-derived restraints are calculated from related protein structures, which correspond to all but the last sequence in the alignment (the target). These templates are read from coordinate files, which are the only data files required. All restraints are added to the existing restraints, even if they duplicate them (but see the comment for the 'OMEGA' restraints below).

Stereochemical restraints:

• 'BOND'. This calculates covalent bond restraints (harmonic terms). It relies on the list of the atom-atom bonds for MODEL, prepared previously by the GENERATE_TOPOLOGY command. The mean values and force constants are obtained from the parameter library in memory. Only those bonds are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'ANGLE'. This calculates covalent angle restraints (harmonic terms). It relies on the list of the atom-atom-atom bonds for MODEL, prepared previously by the GENERATE_TOPOLOGY command. The mean values and force constants are obtained from the parameter library in memory. Only those angles are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'DIHEDRAL'. This calculates covalent dihedral angle restraints (cosine terms). It relies on the list of the atom-atom-atom-atom dihedral angles for MODEL, prepared previously by the GENERATE_TOPOLOGY command. The minima, phases, and force constants are obtained from the parameter library in memory. Only those dihedral angles are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'IMPROPER'. This calculates improper dihedral angle restraints (harmonic terms). It relies on the list of the improper dihedral angles for MODEL, prepared previously by the GENERATE_TOPOLOGY command. The mean values and force constants are obtained from the parameter library in memory. Only those impropers are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'STEREO'. This implies all 'BOND', 'ANGLE', 'DIHEDRAL', and 'IMPROPER' restraints.

• 'MRFP_BOND'. Similar to 'BOND' except that spline restraints from the corresponding MRFP entries in the parameter library are used instead of the harmonic terms. Only those bonds are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'MRFP_ANGLE'. Similar to 'ANGLE' except that spline restraints from the corresponding MRFP entries in the parameter library are used instead of the harmonic terms. Only those angles are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'MRFP_DIHEDRAL'. Similar to 'DIHEDRAL' except that spline restraints from the corresponding MRFP entries in the parameter library are used instead of the cosine terms. Only those dihedral angles are restrained that have all or at least RESTRAINT_SEL_ATOMS in the selected atom set 1.

• 'MRFP_STEREO'. This implies all 'MRFP_BOND', 'MRFP_ANGLE', and 'MRFP_DIHEDRAL' restraints.

• 'SPHERE14'. This constructs soft-sphere overlap restraints (lower harmonic bounds) for atom pairs separated by exactly three bonds (1-4 pairs). It relies on atom radii from the '$RADII14_LIB' library. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion.

• 'LJ14'. This constructs 1-4 Lennard-Jones restraints using the modified 1-4 Lennard-Jones parameters from the CHARMM parameter library. There is no way to calculate 'LJ14' as dynamic restraints. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion.

• 'COULOMB14'. This constructs 1-4 Coulomb restraints by relying on the atomic charges from the CHARMM topology library. There is no way to calculate 'COULOMB14' as dynamic restraints. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion.

• 'SPHERE'. This constructs soft-sphere overlap restraints (lower harmonic bounds) for all atom pairs that are not in bonds, angles, dihedral angles, improper dihedral angles, nor are explicitly excluded by the 'E' entries read from a restraint file or added by the ADD_RESTRAINT command. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion. Note that this makes these restraints static (i.e., not dynamic) and that you must set DYNAMIC_SPHERE to off before evaluating the molecular pdf if you want to avoid duplicated restraints. These restraints should usually not be combined with the Lennard-Jones ('LJ') restraints.

  When INTERSEGMENT is on, the inter-segment non-bonded restraints are also constructed; otherwise, the segments do not feel each other via the non-bonded restraints. This option does not apply to the OPTIMIZE command where information about segments is not used at all (i.e., OPTIMIZE behaves as if INTERSEGMENT = on).

• 'LJ'. This constructs Lennard-Jones restraints for all atom pairs that are not in bonds, angles, dihedral angles, improper dihedral angles, nor are explicitly excluded by the 'E' entries read from a restraint file or added by the ADD_RESTRAINT command. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion. Note that this command makes the non-bonded restraints static (i.e., not dynamic) and that you must set DYNAMIC_LENNARD to off before evaluating the molecular pdf if you want to avoid duplicated restraints. Note that CHARMM uses both 'LJ14' and 'LJ'. For large molecules, it is better to calculate 'LJ' as dynamic restraints because you can use distance cutoff CONTACT_SHELL in OPTIMIZE to reduce significantly the number of non-bonded atom pairs.

• 'COULOMB'. This constructs Coulomb restraints for all atom pairs that are not in bonds, angles, dihedral angles, improper dihedral angles, nor are explicitly excluded by the 'E' entries read from a restraint file or added by the ADD_RESTRAINT command. Only those non-bonded pairs are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. They must also satisfy the RESIDUE_SPAN_RANGE & RESIDUE_SPAN_SIGN criterion. Note that this command makes the non-bonded restraints static (i.e., not dynamic) and that you must set DYNAMIC_COULOMB to off before evaluating the molecular pdf if you want to avoid duplicated restraints. Note that CHARMM uses both 'COULOMB14' and 'COULOMB'. For large molecules, it is better to calculate 'COULOMB' as dynamic restraints because you can use distance cutoff CONTACT_SHELL in OPTIMIZE to reduce significantly the number of non-bonded atom pairs.

• 'ALPHA'. This makes restraints enforcing an $\alpha$-helix (mainchain conformation class ``A'') for the residue segment specified by the two RESIDUE_IDS (Section 2.4.1). The helix is restrained by $\Phi, \Psi$ binormal restraints, N-O hydrogen bonds, ${C}_\alpha$-${C}_\alpha$ distances for $i-j \in \{2-9\}$, ${C}_\alpha$-O distances for $i-j \in \{2-9\}$, and O-O distances for $i-j \in \{2-6\}$. These target distances were all obtained from a regular $\alpha$-helix in one of the high-resolution myoglobin structures. A convenient way to add 'ALPHA', 'STRAND', or 'SHEET' restraints to the calculation by the 'model' script is to include them in the special_restraints routine (Section 1.8, Question 19). Note that at least the non-hydrogen mainchain atoms topology model is required although the same functionality could also be provided for the ${C}_\alpha$-only topology with small changes to the source code.

• 'STRAND'. This makes restraints enforcing an extended strand conformation for the residue segment specified by the two RESIDUE_IDS (Section 2.4.1). This is achieved by applying $\Phi, \Psi$ binormal restraints only. These binormal restraints force the mainchain conformation into class ``B'', except for the Pro residues which are restrained to class ``P'' [Šali & Blundell, 1993].

• 'SHEET'. This calculates H-bonding restraints for a pair of $\beta$-strands. ATOM_IDS specifies the two atom identifiers (Section 2.5.1) defining the first H-bond in the $\beta$-sheet ladder. SHEET_H-BONDS specifies the number of H-bonds to be added. The parallel and anti-parallel sheets are selected by a positive and negative integer in SHEET_H-BONDS, respectively. In a parallel sheet, hydrogen bonds start at the first or the second term of the following series (depending on ATOM_IDS): 1N:1O, 1O:3N, 3N:3O, 3O:5N, etc. For an anti-parallel sheet, the corresponding series is 1N:3O, 1O:3N, 3N:1O, 3O:1N, etc; note that the residue indices are always decreasing for the second strand. The extended structure of the individual strands must be enforced separately by the 'STRAND' restraints if so desired.

• 'USER_DISTANCE'. This makes distance restraints between pairs of atoms from set 2 and 3 (inter-set only), using the value of RESTRAINT_PARAMETERS. Only distances satisfying the RESIDUE_SPAN_RANGE criterion are restrained. This command is useful for making non-specific ``compactization'' restraints.

Homology-derived restraints:

• 'DISTANCE'. This makes distance restraints that are generated for all pairs of atoms $i,j$ where atom $i$ is from selected set 2 and atom $j$ is from selected set 3 (as defined by the PICK_ATOMS command). The atoms also have to be within the residue spanning range specified by RESIDUE_SPAN_RANGE = r1 r2, such that the residue index difference $r1 \le \vert ir2 - ir1\vert \le r2$ when RESIDUE_SPAN_SIGN = off and $r1 \le (ir2 - ir1) \le r2$ when RESIDUE_SPAN_SIGN = on. Moreover, for a restraint to be created, at least one distance in the template structures must be less than MAXIMAL_DISTANCE (in ). The mean of this basis pdf is equal to the template distance and its standard deviation $\sigma$ is calculated from an analytic model specified by DISTANCE_RSR_MODEL. Use model 5 for ${C}_\alpha$-${C}_\alpha$ distances and model 6 for N-O distances. For models 1 through 6, this standard deviation is transformed by $\sigma' = a + b*(\sigma+W_{g})$ where $a$ and $b$ are given by RESTRAINT_STDEV and $W_{g}$ is a gap weighting function of the form $W_{g} = 0.6 * \max(0, 4-g_{av})$. $g_{av}$ is the average distance of the two residues involved in the restraint from a gap. For models 3 through 6, this is additionally transformed by $\sigma'' = \sigma' + \sum_{i}[d+e*\max(0,f-g_{i})]$ where the sum is over each of the atoms $i$ involved in the distance, $d$ $e$ and $f$ are given by RESTRAINT_STDEV2, and $g_{i}$ is the distance of each residue from a gap. The first six models are polynomials and depend on several structural features of the template and its similarity to the target. The polynomial coefficients are specified in library file '$PARAMS_LIB'. When ``polynomial model'' 7 is selected, the standard deviation of restraints is set to constant $a$. Each basis pdf in the distance pdf corresponds to one template structure with an equivalent distance. The weights of basis pdf's depend on local sequence similarity between the target and the templates when BASIS_PDF_WEIGHT = 'LOCAL' and on global sequence identity when BASIS_PDF_WEIGHT = 'GLOBAL'. In addition, the atom pairs restrained by homology-derived restraints must by default not be in a chemical bond, chemical angle, dihedral angle, or on an excluded pairs list. This behavior can be changed by resetting EXCL_LOCAL (see OPTIMIZE).

• 'PHI-PSI_CLASS', 'CHI1_DIHEDRAL', 'CHI2_DIHEDRAL', 'CHI3_DIHEDRAL', 'CHI4_DIHEDRAL', 'PHI_DIHEDRAL', 'PSI_DIHEDRAL', 'OMEGA_DIHEDRAL', 'PHI-PSI_BINORMAL' are the mainchain and sidechain dihedral angle restraints. Only those dihedral angles are restrained that have all or at least NONBONDED_SEL_ATOMS in the selected atom set 1. The means and standard deviations for the dihedral Gaussian restraints are obtained from the $RESDIH_LIB and $MNCH?_LIB libraries and their weights from the MDT tables, which are read in as specified by MDT_LIB in $LIB/libs.lib. The large MDT tables give the conditional weights for each possible dihedral angle class, as a function of all possible combinations of features on which a particular class depends. If DIH_LIB_ONLY is ON or there is no equivalent residue in any of the templates, the weights for the dihedral angle classes depend only on the residue type and are obtained from the '$RESDIH_LIB' and '$MNCH?_LIB' libraries; the DIH_LIB_ONLY argument allows one to force the calculation of the ``homology-derived'' mainchain and sidechain dihedral angle restraints that ignore template information. BASIS_PDF_WEIGHT has the same effect as for the distance pdf's. MDT_LIB_FILE and BIN_LIB_FILE have to be specified for all homology-derived restraints that depend on the MDT files, including all mainchain and sidechain dihedral angle restraints. When MODELLER's 'OMEGA' restraints are calculated, the currently existing restraints on atoms 'O C +N +CA' in all residues are automatically deleted. These deleted restraints correspond to the improper dihedral angles involving the $\omega$ atoms. They are deleted because they could be ``frustrated'' by the new 'OMEGA' restraints. No action is taken with regard to any of the previously existing, possibly duplicated dihedral angle restraints. Thus, to avoid restraint duplication, including that of the 'OMEGA' restraints, call the CONDENSE_RESTRAINTS command after all the restraints are calculated.

BASIS_RELATIVE_WEIGHT is the cutoff for removing weak basis pdf's from poly-Gaussian feature pdf's: a basis pdf whose weight is less than the BASIS_RELATIVE_WEIGHT fraction of the largest weight is deleted.

Example:

# Example for: MAKE_RESTRAINTS, SPLINE_RESTRAINTS, WRITE_RESTRAINTS

# This will compare energies of bond length restraints expressed
# by harmonic potential and by cubic spline.

SET OUTPUT_CONTROL = 1 1 1 1 1

READ_TOPOLOGY   FILE = '$(LIB)/top_heav.lib'
READ_PARAMETERS FILE = '$(LIB)/par.lib'
READ_MODEL FILE = '1fas', MODEL_SEGMENT = '1:' '61:'
SEQUENCE_TO_ALI ATOM_FILES = '1fas', ALIGN_CODES = '1fas'
SEQUENCE_TO_ALI ADD_SEQUENCE = on, ATOM_FILES = ATOM_FILES '1fas.ini', ;
                ALIGN_CODES = ALIGN_CODES '1fas-ini'
GENERATE_TOPOLOGY SEQUENCE = '1fas-ini'
TRANSFER_XYZ
BUILD_MODEL INITIALIZE_XYZ = off
WRITE_MODEL FILE '1fas.ini'

MAKE_RESTRAINTS RESTRAINT_TYPE = 'bond'
WRITE_RESTRAINTS FILE = '1fas-1.rsr'
ENERGY DYNAMIC_SPHERE = off

SPLINE_RESTRAINTS SPLINE_RANGE = 5.0, SPLINE_DX = 0.005, SPLINE_SELECT = 3 1 1
CONDENSE_RESTRAINTS
WRITE_RESTRAINTS FILE = '1fas-2.rsr'
ENERGY