Contents
Introduction
Reference Guide
ICM options
Editing
Graph.Controls
Alignment Editor
Constants
Subsets
Molecules
Selections
Regexp
Tree cluster
Arithmetics
Flow control
MolObjects
Energy Terms
Integers
Reals
Logicals
Strings
Preferences
Tables
Other
Chemical
Smiles
Soap
Gui programming
Commands
Functions
Macros
AlignSS
AlignTwoSequences
Buildpep
CalcArea
CalcBindingEnergy
CalcDihedral4atoms
CalcDihedralAngle
CalcEnsembleAver
CalcMaps
CalcPepHelicity
CalcProtUnfoldingEnergy
CalcRmsd
calcSeqContent
ConvertObject
IcmCavityFinder
DsCellBox
FindSymNeighbors
DsCharge
DsChem
DsCustom
DsCustomFull
DsPropertySkin
CalcEnergyStrain
Calc_nosauc
chemSuper3D
icmPmfProfile
dsPrositePdb
DsRebel
DsSeqPdbOutput
dsSkinLabel
DsPocket
dsStackConf
dsVarLabels
ds3D
dsWorm
DsXyz
Find_related_sequences
findFuncMin
findFuncZero
MakeAxisArrow
modifyGroupSmiles
Morph2tz
nice
cool
homodel
loadEDS
loadEDSweb
makeIndexChemDb
makeIndexSwiss
MakePdbFromStereo
mkUniqPdbSequences
plot2DSeq
plotSeqDotMatrix
plotSeqDotMatrix2
plotBestEnergy
plotOldEnergy
plotFlexibility
plotCluster
plotMatrix
PlotRama
plotRose
plotSeqProperty
predictSeq
prepSwiss
printFast
printMatrix
printPostScript
printTorsions
RefineModel
regul
rdBlastOutput
rdSeqTab
readPdbList
remarkObj
searchPatternDb
searchPatternPdb
searchObjSegment
searchSeqDb
searchSeqPdb
searchSeqPdb
searchSeqSwiss
setResLabel
sortSeq
undsCharge
makeSimpleModel
makeSimpleDockObj
searchSeqProsite
ParrayToMol
ParrayTo3D
Convert2Dto3D
Convert3Dto3D
MakePharma
IcmMacroShape
IcmPocketFinder
Files
User's Guide
References
Glossary
Index

[ AlignSS | AlignTwoSequences | Buildpep | CalcArea | CalcBindingEnergy | CalcDihedral4atoms | CalcDihedralAngle | CalcEnsembleAver | CalcMaps | CalcPepHelicity | CalcProtUnfoldingEnergy | CalcRmsd | calcSeqContent | ConvertObject | IcmCavityFinder | DsCellBox | FindSymNeighbors | DsCharge | DsChem | DsCustom | DsCustomFull | DsPropertySkin | CalcEnergyStrain | Calc_nosauc | chemSuper3D | icmPmfProfile | dsPrositePdb | DsRebel | DsSeqPdbOutput | dsSkinLabel | DsPocket | dsStackConf | dsVarLabels | ds3D | dsWorm | DsXyz | Find_related_sequences | findFuncMin | findFuncZero | MakeAxisArrow | modifyGroupSmiles | Morph2tz | nice | cool | homodel | loadEDS | loadEDSweb | makeIndexChemDb | makeIndexSwiss | MakePdbFromStereo | mkUniqPdbSequences | plot2DSeq | plotSeqDotMatrix | plotSeqDotMatrix2 | plotBestEnergy | plotOldEnergy | plotFlexibility | plotCluster | plotMatrix | PlotRama | plotRose | plotSeqProperty | predictSeq | prepSwiss | printFast | printMatrix | printPostScript | printTorsions | RefineModel | regul | rdBlastOutput | rdSeqTab | readPdbList | remarkObj | searchPatternDb | searchPatternPdb | searchObjSegment | searchSeqDb | searchSeqPdb | searchSeqPdb | searchSeqSwiss | setResLabel | sortSeq | undsCharge | makeSimpleModel | makeSimpleDockObj | searchSeqProsite | ParrayToMol | ParrayTo3D | Convert2Dto3D | Convert3Dto3D | MakePharma | IcmMacroShape | IcmPocketFinder ]

alignSS seq_1 seq_2 s_name ("ali1") R_weights ({1.6 1.8}) i_window (3) l_mute (no)

pairwise sequence alignment that takes into account two additional properties of sequence the secondary structure and the residue accessibility. These properties are assigned to a sequence if it is extracted from a 3D object with secondary structure and precalculated surface area. Example:

read pdb "1crn" 
assign sstructure # makes correct assignment according to hydrogen bonds
show surface area
make sequence
show 1crn_a
 >1crn_a crambin; chain: a; engineered: yes
 TTCCPSIVAR SNFNVCRLPG TPEAICATYT GCIIIPGATC PGDYAN
 >
 EEEE__HHHH HHHHHHHHH_ __HHHHHHHH _EEEE_____ ______
 >#
 4100336502 4405513775 2534500761 3024194673 386254  # compressed accessibility number. 0 - buried, 9 fully exposed

The normal sequence alignment (see align or Align ) will then be biased according to two weights ( the R_weights array) for the alpha-alpha and beta-beta match accordingly. The default values, 1.6 and 1.8, were optimized on a structural alignment benchmark. The i_window parameter determines smoothing of the edges of the secondary structures with the Smooth function (see the code of the macro).

Examples:

read pdb "2rh1" # beta 2 adrenergic
read pdb "1f88" # rhodopsin
delete a_*.!1   # leave only the main chains
show area surface a_1.
show area surface a_2.
assign sstructure a_*.
make sequence a_*.1
alignSS 2rh1_a 1f88_a {1.8,1.6} "ali3d" 3 no 

See also:

• align 3D : structure derived alignment
• Align
• Smooth

alignTwoSequences : interface macro to the `Align function

alignTwoSequences seq_1 seq_2 s_aliName s_comp_matrix ("") s_alignmentAlgorithm ("ZEGA") r_GapOpen (2.4) r_GapExtension (0.15) i_maxPenalizedGap (99)

A macro to provide interface to the Align( seq1 seq2 .. ) function and allow to change global parameters influencing its behavior. Arguments:

• two sequences
• s_alignmentName
• s_comp_matrix ("default"|"gonnet"|"blosum45"|"blosum50"|"blosum62"|"dna"|"hssp"|"ident")
• s_alignmentAlgorithm ("ZEGA"|"H-align")
• r_Gap_Open (2.4)
• r_Gap_Extension (0.15)
• i_maxPenalizedGap (99)

read sequence "seqs"
alignTwoSequences Azur_Alcde Azur_Alcfa "ali2" "blosum45" "H-align" 2.6 0.1 99

buildpep: Building peptides from a sequence

buildpep s_seq

Note: this macro is obsolete. It is superceded by the build string command, e.g.

build string "ala his trp"

calcArea as_

calculates solvent accessible area of each selection in multiple objects and stores it in a table. If a molecule is specified in a multi-molecular object, the surface area of an isolated molecule is calculated and other molecules are ignored. The area is reported in square Anstroms and the probe radius is assumed to be waterRadius .

Output: the macro creates table AREA . The empty comment field is added for user's future use. If the table exists, new rows are appended. Example:

 read pdb "1crn"
 read pdb "2crn"
 calcArea a_*.1  # calculate area around 1st molecule in each object:
 show AREA
 #>T AREA
 #>-Selection---Total_Area--Comment----
    a_1crn.1    2975.9      ""         
    a_2crn.1    4681.2      ""         

See also:

• show area surface as1 [ as2 ] [ waterRadius=.. ] : the main command used in this macro. This command gives larger flexibility since it allows to define the second selection of the vicinity for the calculation.
• surface area
• waterRadius

calcBindingEnergy: estimates electrostatic, hydrophobic and entropic binding terms

calcBindingEnergy ms_1 ms_2 s_terms ("el,sf,en")
evaluates energy of binding of two complexed molecules ms_1 and ms_2 s_terms for the given set of energy terms s_terms. This macro uses the boundary element algorithm to solve the Poisson equation. The parameters for this macro have been derived in the Schapira, M., Totrov, M., and Abagyan, R. (1999) paper.
Example:

 
 read object s_icmhome+"complex" 
 cool a_ 
 calcBindingEnergy a_1  a_2  "el,sf,en" 

 
 build string "ala his his"  
 display atom label 
 calcDihedral4atoms a_/3/nd1 a_/3/cg a_/3/cd2 a_/3/ne2 
 Angle=  -0.06781 deg. (also saved in ) # it is almost flat 

 
 build string "ala his his"  # we use another macro here 
 display atom labels 
 calcDihedralAngle a_/2/cg,nd1,cd2 a_/3/cg,nd1,cd2 
 Angle=  131.432612  deg. (in ). 

 
 build string "ala his his" 
 set vrestraint a_/*  # impose rotamer probabilities 
 mncallsMC = 5000 
 montecarlo           # a stack is formed with energies 
 calcEnsembleAver 300. "Value(v_/2/phi)"    

 
 read object s_icmhome+"crn" 
 calcMaps "crn" Box( a_/15 4. ) 0.6 
 read map "crn_ge" 
 rename m_crn_ge m_ge  
 display m_ge {1 2 3 0 4 5 6} 
# the maps can be used in another session  

 
% _folding  # run the _folding script with the trajectory option. 
% icm 
 read object "mypep"  # the name of your peptide object 
 calcPepHelicity "mypep" 600. 

 
read sequence s_icmhome+"seqs" 
calcSeqContent "*"   # matches names of all sequences 
 .. 
 Statistics for 3 sequence(s): Azur_Alcde Azur_Alcfa Azur_Alcsp 
 AA   N   %   Expected  
 A   42 10.34   7.85 
 C    9  2.22   2.55 
 ... 
 
calcSeqContent "*de"  # sequences ending with 'de' 
 Statistics for 1 sequence(s): Azur_Alcde 
 Res  N   %   Expected  
 A   20 13.42   7.85 
 C    3  2.01   2.55 
 D    8  5.37   5.17 
 E    6  4.03   6.95 

1. One-letter amino-acid code
2. The total occurrence of the amino acid
3. Relative percentage occurrence in the given set of sequences
4. Expected mean occurrence of the amino acid in proteins

[ clusterChemObjFiles ]

• l_delete_water (yes) : automatically deletes water
• l_optimize_hydrogens ( no ) : performs global optimization of hydrogens for best hydrogen bonding network
• l_replace_the_original ( no ) : keeps the same name as the original object and deletes it
• l_display ( no ) : displays the converted object

• deletes water molecules (includes Deuteriorated water) if the 1st argument is yes
• deletes the secondary alternative positions of atoms marked in the PDB (note that sometimes the alternatives are not marked and are deposited as concurrent independent molecules, e.g. two overlapping ligands in "1abe" )
• it will built hydrogens based on residue library ( icm.res ) or valency/formal charge rules.
• delete ambiguous covalent bonds with some metals according to the ICM and MMFF force field (e.g. around Fe ).
• assign formal charge of -1 to atoms of MMFF type 4 and nitrogens next to Fe and deprotonate then accordingly
• fix atoms of type 226 and MMFF type 15 around Zn (includes deprotonated Cysteines).
• assign MMFF and ICM atom codes, and partial charges using the formal charges, MMFF types and bond charge increment scheme.
• if heavy atoms that were missing in the PDB (due to the lack of density), they will be added according to the residue name and assigned zero occupancies.
• in the converted object,
• the following residues will be further optimized:
  • His : three protonation states and two rotations will be tried and the residue will be renamed according to its subtype: hie (epsilon tautomer) or hip (+)
  • Asn and Gln (a 180 deg. flip will be tried)
  • Cys in the vicinity of Zn, Cu, Fe and Co to cym
• if the 2nd argument is yes : (i) the atoms that were missing and/or atoms with occupancies ≤ 0.1 will be globally optimized to avoide clashes. (ii) the hydrogens will be systematically rotated for best energy

Output:

• the converted object. The original object is not changed unless the 3rd argument was yes .
• the r_residualRmsd variable

The macro returns r_residualRmsd value containing the Rmsd of the model atoms from the equivalent template atoms (the same value is returned by the convert command in r_out ). If this residual is greater than 0.5 , it usually means some problems with the conversion (e.g. unusual residues, missing parts, etc.).

This macro can be found in the __macro file or viewed using the edit command. It calls two other macros:

• optimizeHisProAsnGlnCys (in _macro file )
• optimizeH_zeroOcc (in _macro file )

Example:

  read pdb "1abe"
  convertObject a_1,2 yes yes yes no
  show r_residualRmsd

calculates and displays cavities in a molecular structure. These cavities are sorted by size, and displayed. The l_interactive argument allows cavities to be displayed one by one interactively. To display the transparent outer shell edit the macro and activate this feature. The r_minVolume parameters defines the volume of the smallest retained cavity. Increase it if you want only large cavities. For each cavity this macro calculates volume V (in square Angstroms), area A and an effective radius R (compare it with the radius of a water molecule of 1.4A).

• a grob with analytical molecular surface ( a.k.a. skin ) of the selected atoms can be built using the make grob skin as_ as_ "g_skin" command.
• this grob can be divided into the separate grobs with the outer shell and all the inner cavities with the split g_skin command.
• icmCavityFinder also uses the Volume(g) and Area(g) functions to measure volume and area of the cavities, as well as the Sphere( g_ r_radius ) function to select atoms and residues around any grob.

 
 read object s_icmhome+"1qoc" 
 delete a_w*  # remove water molecules 
 icmCavityFinder a_1 yes 4. 
   3  deleted 
  Info> finished surface search, n_of surface atoms = 744 
  Surface .................................................. 
  Info> finished basic surface element calculations 
  Info> Estimated vertex number = 335800, actual = 184896 
  Info> packing vertices... sorted... done! 
  Info> skin grob "" created (solid model: 32197 point 
  Info> 3 grobs   ...   created 
 Shell  1: V=11039.291805 A=4525.876702 
  Warning> Volume() may be improperly calculated: env 
 CAVITY 2: V=25.253718 A=44.282805 R~1.710848 -------------- 
 - Num  Res. Type ----{SS Molecule}-- Object - sf - sfRati 
    26  ile   Amino    I H  m            1qoc     0.0  0.00  
    53  leu   Amino    L E  m            1qoc     0.0  0.00  
    58  val   Amino    V _  m            1qoc     0.0  0.00  
    76  val   Amino    V E  m            1qoc     0.0  0.00  
    87  val   Amino    V E  m            1qoc     0.0  0.00  
    89  ile   Amino    I E  m            1qoc     0.0  0.00  
 ... 

 
macro dsCellBox os_ (a_) 
  gCell = Grob ("cell" Cell(os_)) 
  display gCell magenta 
  keep gCell 
endmacro 

Prerequisites and Arguments

• a PDB entry or an icm-object that contains the information about the crystallographic unit cell and symmetry .
• as_ ( default: as_graph ) : a source selection around which the symmetry neighbors are examined.
• r_radius (7.) : the vicinity
• l_append (no) : by default a separate object is created with all transformations. If yes the object with symmetry related atoms is added to the source object
• i_extend_by (2) : if the next argument is no, the residue ranges that are within r_radius will be extended by the specified parameter and all the other (distant) residues will be deleted
• l_keepEntireChain (no) : if this flag is yes the entire chain in which a proximal symmetry related atom is found will be kept, otherwise only the close residues (corrected by i_extend_by) will be kept
• l_display (yes) : displaying the results.

The algorithm

• The entire asymetric unit is multiplied according to the Symgroup
• then 26 additional cells (3*3*3-1=26) are generated around the current one.
• the content is shifted to the 26 cells
• the selection in the r_radius vicinity is make at the residue level and is extended by i_extend_by along the chain.
• either entire molecule ( l_keepEntireChain is yes ) or the fragments are merged to the same object
• the output variables are generated

The output

• a single new object with the symmetry related neighbors (if l_append is no , otherwise it is appended to the existing object )
• nSymNeighbors integer returns the number of symmetry related groups of atoms that were transformed
• R_symTrans cancatenated transformation vector with 1+nSymNeighors sections of 12 elements (see transformation vector ). The first section is identity transformation.
• S_neighborAtoms is a sarray with 1+nSymNeighbors residue selections in each transformation (skip the first one, the self selection)

Example:

read pdb "2ins"
findSymNeighbors a_1,2 5. no 2 no no  # a_2insSym. object with 14 fragments is created.
show nSymNeighbors, S_neighborAtoms
 7
 >S S_neighborAtoms
 a_2ins.1:2,5/*|a_2ins.c/^N21|a_2ins.d/^G8:^S9,^V12:^E13,^Y16,^G20:^K29
 a_2ins.5/*|a_2ins.b/^S9:^H10|a_2ins.c/^L13|a_2ins.d/^V2:^Q4,^L6,^A14,^Y16:^E21
 a_2ins.b/^K29
 a_2ins.5/*|a_2ins.b/^H10
 a_2ins.c/^G1,^E4|a_2ins.d/^P28:^A30
 a_2ins.b/^R22
 a_2ins.c/^A8:^V10|a_2ins.d/^N3,^H5
 a_2ins.c/^G1,^N18:^Y19,^N21|a_2ins.d/^F25,^K29:^A30

 
macro dsCharge 
  display a_*./asp,glu/o?* cpk red 
  display a_*./lys,arg/nz,n?* cpk blue 
endmacro 

 
 build string "trp"      # you need an ICM object  
 tzMethod = "z_only" # tether to the z-plane 
 set tether a_       # each atom is tethered to z=0  
 minimize "tz"       # keep the cov. geometry  

• atom type ( s_coloringType="atom" ),
• residue type ("residue"),
• unique molecules ("molecule"),
• secondary structure type ("sstructure"),
• N-to-C-terminal chain course (NtoC""),
• B-factors ("bfactor"),
• electric charges ("charge"),
• solvent accessibility ("accessibility"),
• residue polarity ("polarity"),
• residue hydrophobicity ("hydrophobicity")

dsPropertySkin as_sel (a_) l_wire (yes) displays essential properties of molecular surfaces which are essential for binding small ligands, peptides or other proteins. The first argument is a selection of atoms involved in the surface calculation. The second argument allows you to display the surface as: skin ( l_wire=no ), or wire ( l_wire=yes )

• white - neutral surface
• green - hydrophobic surface
• red - hydrogen bonding acceptor potential
• blue - hydrogen bonding donor potential

 
 read pdb "1a9e" 
 delete a_w* 
 convert    # convert to ICM for map calculations 
   # select receptor atoms 9. away from the peptide with Sphere 
 cool a_    # display ribbon 
 dsPropertySkin Sphere( a_3 a_1 9. ) yes    
   # adjust clipping planes for better effect 
 write image png 

1. display your ICM object
2. switch selection level to residue (R)
3. select region with selection box or lasso
4. click on the right mouse button over one of the selected residues
5. selected Display and then Property Skin
6. it creates grob g_recSkin which can then be undisplayed and further manipulated

 
 read object s_icmhome + "crn" # an ICM object 
 calcEnergyStrain  a_/A   
 show ENERGY_STRAIN 

calc_nosauc R_scores L_01labels r_score_error (0.) l_linear_auc (no) l_keep_table (no) l_showresults (yes)

compute the normalized measure of the recognition strength of the provided score ( R_scores ) given a matching array of zero and one labels for 'noise' and 'signal' respectively. Lower scores are considered better (comes from energy), invert the sign of the scores otherwise. Example: scores { 2.1 4. 3. 44.} and labels {1 0 0 0} correspond to a perfect recognition since 2.1 is the lowest score.

The normalized measure returns the value of 100. for any perfect separation of signal from noise and values close to zero for a random subset of noise. The normalized measure is based on the area under curve in the following axis: the number of signal records in the top N scores versus the record rank (or the square root of it). The rank is defined as the order in a sorted array. The normalized measure is the following:

AUC..normalized = 100*( AUC - AUC_random )/(AUC_perfect / AUC_random )

Input

• a real array of N Scores R_scores
• an integer array of N zero or one labels
• an error of the score values
• a flag to to calculate the linear version of AUC (the square root is the recommended default, however)
• a flag to keep the resulting table
• a flag to print the NSA values (otherwise

Algorithm

• a table of N scores and N labels is built
• the table is sorted by scores
• a histogram of percentage of signal rows in M best scores is plotted
• the X-axis of the histogram is transformed as follows: X = Sqrt(100.*M/N) (or X = 100.*M/N for the linear version)
• an area under the resulting curve AUC is calculated and divided by the size of the X axis. The resulting number is between 0. and 100.
• the random and the perfect AUC values are calculated
• the normalized value is calculated as: AUC..normalized = 100*( AUC - AUC_random )/(AUC_perfect / AUC_random ) .
• if the r_score_error parameter is greater than zero, the scores are modified with the random gaussian noise and the nosauc values are computed every time. Rms and mean are calculated and stored in the header of the tabauc table.

OutputIf the l_keep_table flag is set to no, the four values are returned as R_out[1:4].

• R_out[1] returns the NSA value
• R_out[2] returns the mean NSA value after the score values have been modified with gaussian noise 35 times
• R_out[3] returns the standard error of the NSA value after introducing the gaussian noise.
• R_out[4] returns the Normalized Median Rank (the median rank from 1 to 100) of the positives.

• tabauc table that can be used to plot the enrichment (if l_keep_table is defined as yes ). It contains arrays: A (labels), S (score) , R (the last randomized score), X (the relative Sqrt(rank) or rank), and N (the cumulative enrichment). Plot N vs X for a AUC plot.
• tabauc.nosauc ( a real value ≤ 100. ) : normalized area under curve in normalized %hits vs sqrt( %rank ) axes. Values around zero or negative are indicative of no recognition. The perfect recognition corresponds to a value of 100.
• nosauc_ave (real) : if r_score_error is not zero, it gives an average nosauc upon many gaussian randomizations of the scores
• nosauc_rms (real) : if r_score_error is not zero, it gives an rmsd of nosauc upon many gaussian randomizations of the scores
• nmr (real) : returns the Normalized [0. to 100.] Median Rank of the positives. E.g. if there are 5 binders and 1000 nonbinders, it will return the rank of the 3rd positive (3 is the median in a set of 5), normalized to a value from 0. to 100.
• type (string) : contains "linear" or "sqrt"

Example:

N=1000; n=100
calc_nosauc Random(0.,1.,n,"gauss")//Random(3.,1.,N-n,"gauss") Iarray(n,1)//Iarray(N-n) 0.2 yes no
show R_out
show tabauc.nosauc, tabauc.nmr
# select columns X and N and plot the enrichment curve.
# play with the parameters

chemSuper3D

chemSuper3D os_in os_template l_optimize (no) l_display (no) l_all (no)

performs a sequential flexible superposition of multiple molecules in the os_in selection on a single rigid template os_template . For static superposition, use superimpose chemical .

Prerequisites and Input

• several objects with chemical hetatm molecules
• os_in : contains one molecule per object

Parameters and options

• l_all - option of the find molecule sstructure command. By default l_all = no only one largest match is used.
• l_optimize - currently inactive
• l_display - displays the result

Output

• Flexible molecules superimpowed on the template.

See also:

• superimpose ( superimpose chemical for rigid superposition)
• find molecule sstructure (find the maximal common substructure )

icmPmfProfile

macro icmPmfProfile os_ ( a_ ) l_accessibilityCorrection (yes) l_display ( no ) calculates a statistical energy of mean-force for each residue of a provided object. This energy is calculated with the "mf" parameters defined in the icm.pmf file. The residue energies are then normalized to the expected mean and standard deviation of the same residue in real high resolution structures. The mean energy value can be calculated as a function of its solvent accessibility if l_accessibilityCorrection is set to yes. The calculated table contains residue energies and accessibilites. These values can be used to color residues of the molecule according to those values. In an example shown here we build a model (using the build model command of HCV protein on the basis of another viral coat protein. Then the profile was calculated for the model and the original structure. The calculation clearly shows the problematic regions of the model (the red parts) while the source structure looks quite reasonable.

dsPrositePdb

dsPrositePdb ms_ (a_*) r_prositeScoreThreshold (0.7) l_reDisplay (no) l_dsResLabels (yes)
Finds all PROSITE pattern-related fragments in the current object and displays/colors the found fragments and residue labels.

dsPocket ms_ligand (a_H [1]) s_GrobName ("") l_overwrite (yes) l_ds_xstick_hb_labels (no)

dsPocketRec ms_ligand (a_H [1]) ms_receptor (a_!H ) r_margin (6.5) s_GrobName ("") l_overwrite (yes) l_ds_xstick_hb_labels (no)

display the receptor pocket around the selected ligand ms_ligand. Only the largest contiguous pocket surrounding the ligand is retained for clarity. Macro also colors the molecular surface by hydrogen bonding potential and hydrophobicity if receptor is as ICM object. Best used with the ligand shown in cpk, if the ligand is small.

The first macro ( dsPocket ) is trying to guess what the selecting of atoms for the binding pocket is. Then it calls dsPocketRec The second macro ( dsPocketRec ) has identical arguments plus explicit receptor selection.

The dsPocket guess about the receptor:This is the order of guesses about the selection of the binding pocket molecules:

1. The macro first tries to see if there is a "receptor" of the ICM type specified by the interactive 3D editor ( the Ligand tab of the GUI tools)
2. Then it tries to get all molecules from the same object as the ligand selection except the ligand and water molecules
3. if step 2 fails, it tries to find the first ICM object among those displayed that is within a 7A vicinity of the ligand

Prerequisites and arugments of the dsPocketRec macro

• a ligand (can be a selection in an object) and selecting of molecules interacting with the ligand. Both ligand and binding pocket can belong to an ICM or non-ICM (raw PDB) objects.
• r_margin : the cutoff distance from the ligand atoms for the pocket calculation
• s_GrobName : the preferred name for the pocket grob object.
• l_overwrite logical will overwrite the previous pocket grob with this name if yes .
• l_ds_xstick_hb_labels logical will display the contact residues in xstick, hydrogen bonds and residue labels

The procedure

• the analytical molecular surface ( aka skin ) is computed as a grob object consisting of triangles.
• the surface is split into contingous grobs and only the largest one is retained.
• coloring: if the "receptor" object is of the non-ICM (PDB or Model) type it will get a uniform lightcyan color.
• coloring for the pockets from ICM objects: the grob is initially colored white. Then some hydrophobic areas are colored green, the hydrogen bond acceptor surfaces as red and the hydrogen bond donors as blue .
• coloring the movable binding pocket side chains. The carbons of movable side chains in the 4A vicinity of the ligand are colored pink .
• the residues in the pocket are labeled.

Output

• the grob (mesh) object with specified name colored by pharmacophoric properties if the selection of binding molecules belonged to an ICM object
• the grob will be displayed as a transparent smooth object. You can change the type of display by right clicking on the display icon in the GUI WorkSpace.

 
 read object s_icmhome+"complex" 
 cool a_ 
 dsPocket a_1 "" yes  # shows the surface of a_1 

This macro replaces dsSkinPocket and dsSkinPocketIcm macros.

ds3D M_interObjectDistances [S_names] display 3D coordinates corresponding to an input square distance data matrix. Relative errors (in percent) of embedding to 3D space are in R_out: first entry is for the total error, next three are for X, Y and Z coordinates.
	Representation of inter-sequence evolutionary distances in three-dimensional space

 
 build string "ala his trp" 
 mxyz = Xyz( a_ 5. surface ) 
 display skin white 
 dsXyz mxyz   
 color a_dots. red 

find_related_sequences macro: identify similar and superimposable chains in multiple objects

find_related_sequences ms_ (a_*.A)

identifies pairs of molecules (chains) with similar sequences in the input selection. Input and arguments

• one or several objects with two or more amino-acid chains (molecules)
• a selection of more than one molecules with more than five amino-acids

* for each pair of amino-acid chains in all objects the following:

1. extract sequences and align them using alignMethod ="ZEGA", record sequence identity ( seqid )
2. superimpose them by using this alignment and calculated heavy atom ( rmsd )
3. record all pairs with the alignment probability value less than 0.0001 or alignment sequence identity > 90%
4. add a pair to the related_sequences table

Output

• related_sequences table with the following columns: name1 name2 len1 len2 seqid rmsd consensus
• the table is active: if you double click on a pair two related chains will be selected

Example:

read pdb "1arb"
read pdb "1arc"
find_related_sequences a_*.*
show related_sequences

 
findFuncMin "Sin(x)*x-1." , -1. 2. 0.00001 
 -1.000000 < x < 0.500000 
 -0.250000 < x < 0.500000 
 -0.062500 < x < 0.125000 
 .... 
 -0.000004 < x < 0.000008 
 -0.000004 < x < 0.000002 

 
findFuncZero "x*x*x-3.*x*x" 1. 33. 0.00001 
 => x=17.000000  F=4046.000000 
 => x=9.000000  F=486.000000 
 => x=5.000000  F=50.000000 
 => x=3.000000  F=0.000000 

Determining selection axis and making an arrow.

makeAxisArrow rs_ ( a_/10:18 ) i_length (10) r_radius ( 0.12 ) r_head_width_ratio ( 2. )

this macro determines the direction make an arrow with specified parameters. Input and arguments:

• rs_ a contiguous residue selection (usually a strand or a helix, but it will work anyway).
• i_length (10) : if 0 is specified the length will be determined from the selection
• r_radius ( 0.12 ): arrow radius in Angstroms (see GROB.arrowRadius )
• r_head_width_ratio ( 2. ) : relative expansion of the arrow radius for the arrow head (see GROB.relArrowHead )

• an average helical angle is reported
• a grob with name starting from "axis_" and molecule name , e.g. axis_m

read pdb "1crn"
display ribbon
makeAxisArrow a_/23:30 10 0.2 2.1
color axis_m blue

modifyGroupSmiles

modifyGroupSmiles as_ancor s_GroupSmile l_reset_MMFF_types (yes) l_reassign_MMFF_charges (yes) l_optimize_geometry (no)

attaches a chemical group to the specified ancor atom. Input and Arguments

• an ICM object of a chemical
• as_ancor : an atom to be modified, frequently a hydrogen. If a heavy atom is specified instead of a specific hydrogen, the first hydrogen will be used to determine the growth direction.
• s_GroupSmile : the attachment point can specified as [atomName*] or just as *. The first atom is assumed to be the attachment point if the attachment is not explicitly specified. Example smiles: "C[C*](C=O)O" (the second atom is the attachment point), "C(C=O)O" the first carbon is taken.
• l_reset_MMFF_types (yes) : flag to rest the types for all atoms in the molecule
• l_reassign_MMFF_charges (yes) : reassign the chages
• l_optimize_geometry (no) : uses MMFF minimization to improve geometry

Output

• Modified molecule

morph2tz : generating sterically plausible intermediate conformation for conformational morphing

morph2tz rs_loop ( a_/ ) i_nIter l_store_in_object (no) l_play_morph (yes)

this macro generates a stack of intermediate conformations for an fragment in an object. This intermetidate conformations are obtained by a restrained minimization using the source and target structures, as well as the steric restrains.

Prerequisites and arguments

• an ICM object in which a subset of atoms (including a special case of all atoms) is tethered to atoms in a different destination object. For example a DFG-in loop in a kinase tethered to a DFG-out conformation in another object. This set up can be prepared with the "modeler's view" GUI tool.
• the rs_loop fragment of an ICM object (e.g. a_a/394:406 )
• i_nIter is the number of intermediate conformations requested to be generated. Since the resulting stack of conformers can further be interpolated using the l_play_morph option ( and after the macro with the display stack command), this number does not need to be very big, say 10 to 50.
• l_store_in_object (no) : this flag determines if the stack at the end is also stored inside the object. The default action is to generate a common stack .
• l_play_morph (yes) : if yes the generated stack will be played in an interpolated fashion using the display stack command.

The algorithm

• the key point is to have the destination coordinates compatible with the coordinates of the regions flanking the selection
• the coordinates before and after the selected fragment are kept as is.
• each intermediate conformation is generated by minimizing the van der Waals and torsion energy and differently weighted restrains to the source and destination coordinates. The energy terms used are the following "vw,14,to,ts,tz,rs" . Feel free to modify this command it you can tolerate a longer calculation and care about the quality of the intermediate conformations.
• the generated minimized conformers are stored in the conformational stack
• further interpolation between them can be done with the display stack command.

The output

• The default output is a stack of conformations with i_nIter minimized intermediate conformations between the start and the finish.
• If l_store_in_object flag was yes , the stack is also compressed and copied to the object

nice

nice auto s_PdbSelection ("1crn") l_invert_color (no) l_wormStyle (no) l_append (no) l_nodisplay (no)
reads and displays a PDB structure in ribbon representation; colors each molecule of the structure by colors smoothly changing from blue (at N-terminus) to red (at C-terminus). The auto keyword allows to skip N last arguments.
Example:

 
 nice "365d"  # new DNA drug prototype 
 nice "334d"  # lexitropsin, derivative of netropsin 

loadEDS s_pdbcode ("1mui") r_sigma_contour_level (0.)

read the map file with crystallographic electron density from one of three sources. The map named m_s_pdbcode (e.g. m_1crn ) is loaded from the Uppsala server or a local directory. If the macro ends up loading it from the web, it writes the map a local repository as s_pdbcode.map file for fast future access. To read the map file three locations are checked in the following order:

• s_userDir + "/data/eds/" directory.
• TOOLS.edsDir directory. This directory can be shared and have read permissions only.
• the Uppsala EDS server. This is performed with the loadEDSweb macro.

The arguments

• s_pdbcode ("1mui") : 4 letter pdb code. The resulting map will be 1mui.map for that code.
• r_sigma_contour_level (0.) : if not zero, a grob with the electron density contour is created.

The procedure

• the 2Fc-Fo map for the entire crystallographic cell is uncompressed and loaded from a local directory or the server.
• the map is contoured at the specified sigma level if sigma is non-zero. Keep it at zero for speed, unless you need the contours.
• if a pdb object with the same name is present in the directory, ICM will contour only around the atoms of the object instead of creating the grob for the entire crystallographic cell.

The ouput

New files, if the map was downloaded from the web.

• compressed s_pdbcode.map file in TOOLS.edsDir directory if it is write accessible
• alternatively, compressed s_pdbcode.map file in s_userDir + "/data/eds/" directory

• map m_s_pdbcode
• grob g_s_pdbcode
• if matching pdb object is found (and it has some atoms selected), an extra smaller map is created around the selection for interactive sigma-level change.

loadEDSweb

loadEDSweb s_pdbcode ("1mui") [ s_maptype ("2fofc") ] downloads 2fofc (or other s_maptype) map from the Uppsala electron density server "http://eds.bmc.uu.se/"Creates a map object m_s_pdbcode . This macro is used by the loadEDS macro.

Example:

loadEDSweb "1mui" "2fofc"
display m_1mui

 
% icm 
makeIndexChemDb "/data/chem/chemdiv/cdi.sdf" "/data/icm/inx/cdi" "mol" {"ID"} 

• a square matrix of distances between n objects. For arrays it may be calculated with the Distance ( ) function (e.g. Distance(Xyz(a_//ca))). For angular RMSD the distance can be calculated from a matrix v of values of torsion angles for many conformations:

   
   for i=1,n-1 
     di[i,i]=0. 
     for j=i+1,n 
              # takes care of -179 and 181, base 360 is the default 
        dif=Remainder(v[i]-v[j])    
              # angular RMSD 
        di[i,j]=Sqrt(Mean(dif*dif))   
        di[j,i]=di[i,j] 
     endfor 
   endfor 
   di[n,n]=0. 
  

• sarray of names for each of n points . Possibilities:
  • the empty sarray: {""}. No name tags will be attached to each point
  • Sarray(Count(n)) generates names like this: {"1" "2" "3" ... }
  • user-defined: e.g. Name(a_*.) if each point correspond to an object
  • manual: e.g. {"A" "compound X" "c"}
• See also: arguments for the plot command.

generates a residue table and three interactive plots for non-glycines, glycines and omega angles (see Tools/Analysis menu)

plotRamaEps rs_ l_show_residue_label (no) l_shaded_boundaries (yes)
generates a phi-psi Ramachandran plot of an rs_ residue selection. If logical l_show_residue_label is on, the macro marks the residue labels. If l_shaded_boundaries is on, the allowed (more exactly, core) regions are shown as shaded areas; otherwise the contours of the core regions are drawn.

 
 read pdb "1crn" 
 make sequence  
 b = Bfactor( a_/* ) 
 plotSeqProperty b String(1crn_m ) {"" "" ""} "tm.eps" 20 "portrait"       

• side-chain sampling using montecarlo fast
• interative annealing with tethers you have provided
• second side-chain sampling to resolve the new problems resulting from the second step

 
 searchPatternPdb "^[LIVAFM]?\{115,128\}[!P]A$"  

 
 read sequence "zincFing.seq" # load sequences   
 find prosite 2drp_d            # search all < 1000 patterns 
                                # through the sequence  
 find profile 2drp_d            # search profile from prosite database 

parrayToMol macro

parrayToMol chemarray

This macro converts each elements of chemarray to a 3D object preserving coordinates

Example:

 parrayToMol Chemical("CCCCC")

See also: parrayTo3D convert2Dto3D

parrayTo3D macro

parrayTo3D chemarray

This macro converts each elements of chemarray to a 3D object optimizing geometry.

Example:

 parrayTo3D Chemical("CCCCC")

See also: parrayToMol convert2Dto3D

convert2Dto3D macro: converting molecules from a 2D mol file or chemical spreadsheet to optimized 3D object(s)

convert2Dto3D os_obj l_build_hydrogens (yes) l_fixOmegas (yes) l_display (no) l_overwrite (yes)

the main macro that is used to convert 2D molecules from an .sdf or .mol file to a full atom optimized ICM 3D object. It is used by many ICM tools and scripts (multiple superpositions, conformational generator, docking etc.).

Prerequisites and arguments

• one or several loaded objects, os_obj . It can be obtained from a 2D mol file or ICM chemical table T by the following commands: read mol or read mol input=String( T.mol[i] ) name = s_objName (for table T and element i ).
• l_build_hydrogens (yes) : if yes it adds hydrogens according to the valency rules and formal charges. The user needs to check the bond orders and set the formal charges if needed
• l_fixOmegas (yes) : the an angle of torsion type 3 that is assigned to the peptide bond omega angle and similar angles in chemicals is found, this flag sets the angle to 180. and fixes it at this value. Otherwise it is treated as flexible within the framework of the MMFF force field and its final value is determined by energy minimization and is not guaranteed to be 180.
• l_display (no) : display the resulting object(s)
• l_overwrite (yes) : if yes the macro replaces the input object, otherwise if creates new ones with the name extended with "3D".

• the hydrogens are added to the source object
• the MMFF types and charges are assigned to the atoms
• the omega-like angles ( v_//T3 ) are identified and fixed if the 2nd argument is true .
• the structures are randomized, MMFF minimized and stored in a stack
• the chirality restrained is imposed for chiral centers ( a_//XLR )

Output

• one converted and optimized object for each object in the input selection. If l_overwrite was yes , the names will be preserved. Otherwise "3D" will be added to the object name

See also: parrayTo3D parrayToMol, convert3Dto3D (coordinate-preserving convertion of a 3D mol file)

convert3Dto3D macro: converting a 3D chemical from a chemical spreadsheet or 3D mol/sdf file without changing coordinates

convert3Dto3D os_obj l_build_hydrogens (yes) l_display (no) l_overwrite (yes)

same as convert2Dto3D but the x,y,z coordinates are preserved.

makePharma macro

makePharma as_selection s_resultName l_points l_display

This macro creates a pharmacophore object from as_selection. s_resultName will be used for the result. if l_points is yes pharmacophore will be created (see show pharmacophore type) otherwise input molecule will be split by rotation bonds.

See also: find pharmacophore , pharmacophore

icmMacroShape: generating a smooth low resolution surface of a macromolecule.

icmMacroShape as_ i_complexity (8) r_gridStep (0.) r_contourLevel (1.2) l_colorByDepth (yes) l_fast (no) l_display (no)

The icmMacroShape macro generates a low resolution surface

Prerequisites and arguments.

• as_ : the atom/residue/molecule/object selection for which the smooth surface is built
• i_complexity (8) : the number of harmonics retained in the reconstruction of the smooth density. The larger, the more detailed. The minimal complexity is 2.
• r_gridStep (0.) : the step used in calculating the density and reconstruction. The zero default value means that the grid size will be adjusted automatically for large objects to avoid exceedingly large grid maps and transformations.
• r_contourLevel (1.2) : the density level at which the transformed density is contoured to generate a smooth surface. The lower value will result in the larger (looser) surface envelope.
• l_colorByDepth (yes) : assigns color according to the lower (than i_complexity) resolution map
• l_fast (no) : uses a faster generator of the electron density, but compromises the true shape of electron density.
• l_display (no) : displays the result if yes . Currently the surface is displayed as transparent solid smooth. The display can be changed from GUI using the right-click on the grob display icon or by editing the text of the macro.

The algorithms follows these steps:

• generate an electron density using a 2-exponential approximation of an atomic density ( l_fast logical allows to activate a faster but less rigorous method ). The grid size is controleed by the first real parameter. If it is zero, the grid size is determined automatically.
• perform a Fourier transformation of the electron density
• truncate high frequency harmonics ( the i_complexity parameter determines the number of harmonics used in reconstruction )
• generate a new electron density at lower resolution
• contour this electron density at the specified level ( default 1.2 )

The output

• a grob (mesh) object with a four-part name is built. The parts: "shape_" + objectName + size + complexity

icmPocketFinder macro

icmPocketFinder as_receptorMol r_threshold ( 4.6 ) l_displayPocket (yes) l_assignSites (no)

Use this macro to find binding pocket(s) for the input as_receptorMol.

Arguments:

• r_threshold: tolerance level. The lower the tolerance value the more pockets predicted and the higher the tolerance the less pockets predicted
• l_displayPocket: display the first found pocket
• l_assignSites: create sequence sites if you wish the site to be labeled.

The macro creates a table which contains a list of all pockets found. The table is sorted by pocket volume.

Example:

read pdb "2hiw"
convertObject a_ yes no yes yes
icmPocketFinder a_1 4.6 yes no
show POCKETS