ABangle. A program to calculate and analyse the orientation between the VH and VL domains in 
Antibodies. 

J. Dunbar, A. Fuchs, J. Shi, CM. Deane, ABangle: Characterising the VH-VL orientation in antibodies, PEDS, 2013, In Press


Domain orientation is defined using six absolute measures: Five angles and a distance. 
Geometry.png shows the geometrical system used to define the orientations.

HL - torsion angle between L1 and H1 vectors.
LC1   - bend angle between L1 and C.
LC2   - bend angle between L2 and C
HC1   - bend angle between H1 and C
HC2   - bend angle between H2 and C
dc    - the length of the C vector.

Functionality:

~ Calculating orientation angles for a new structure:

    Required Arguments:
    -i                  Input PDB files to be analysed (multiple files allowed). Heavy and light
                        chains must have different chain identifiers. Otherwise, all Fvs within the 
                        file will be automatically identified.


    Optional Arguments:
    -store                      Store the angles, sequence and pdb structure of the Fvs in input PDB file.
                                A local data repository will be created in a path of the user's choosing.
    -change_numbering_path      Change the path to local antibody numbering program. Currently, only
                                compatible with a local copy of abysis. Follow on screen instructions to
                                make online numbering default instead.
    -online                     Use the ABnum Public Server to chothia number the structures in 'i' argument.
    -usernumbered               Use the chothia numbering in the PDB file. In this case, file must contain a 
                                single Fv region with heavy and light chain identifiers being H and L 
                                repectively. The residue identifiers will be taken as Chothia numbered 
                                positions
    -change_data_path           Change the path to the local user data repository.
    -clear                      Clear a structure from the user data repository. Use 'all' to clear all data.
    -scfv                       Chains that are single chain fv structures. ABangle will try to find VH and
                                VL regions within the chain.


    On the first use of the -i option, the user will be asked whether they wish to provide a path to
    a local numbering program. Currently, only abysis is supported for local numbering (path to the 
    script kabnum_wrapper.pl is required). If this program is unavailable to the user, the public
    abnum webserver can be used. To view or change the path to numbering program, use change_numbering_path 
    option.
    The user will also be asked whether they wish to store data. If yes, a new folder named 
    ABangleData will be created in a path of a user's choice. Use change_data_path to change this 
    repository. The data stored is the orientation angles, the sequence of the fvs and a chothia
    numbered pdb file of each Fv region that has been identified by the program.

    Examples:
     1. Find all the Fv regions in a PDB file (or files) and calculate the orientation angles between
        VH and VL domains:
            ABangle -i AB1.pdb
              or
            ABangle -i AB1.pdb AB2.pdb AB3.pdb

     2. Do calculation for all Fvs in all of PDBs in .dat file:                
            ABangle -i ListOfFiles.dat
              where ListOfFiles.dat contains:
                path/to/file/AB1.pdb                
                path/to/file/AB2.pdb
                path/to/file/AB3.pdb
                .       .       .
                .       .       .
              

~ Select sets of structures to analyse.

    Optional Arguments:
    -r                  Specify residue positions. (e.g. H50 or L87). With no other arguments, the
                        combination of amino acids at those positions will be reported. The number
                        of structures (in non-redundant set) with each combination is reported, as 
                        well as the number expected from the frequencies of amino acids at the 
                        individual positions.
    -wa                 Select structures With Amino acids at postions determined in -r argument.  
    -f                  Specify factors to select structures with. Choices are: HL, HC1, LC1, HC2,
                        LC2, dc, Method, Res, Rfac, Bstate, AGtype, Hgroup, Lgroup, 
                        Ltype, Species, L1length, H3length.
    -wp                 Select structures With Parameters of the factors determined in -f argument.
                        See examples.
    -s                  Pick individual structures by name. Use 'mine' to recall all user structures.
                        Use 'all' to pick all pre-calculated structures.
    -target             Select all pre-calculated structures which have a similar domain orientation 
                        of a particular structure. This automatically puts thresholds on each of the
                        angular measures and searches for structures which meet the threshold of each
                        measure. Thresholds are taken as the angle we would expect sequence-identical
                        unbound structures to be within.

    Examples:
     1. Request the combinations of amino acids at postions H40 and L22:
            ABangle -r H40 L22

     2. Request structures with arginine at H40 and serine at L22:
            ABangle -r H40 L22 -wa R S

     3. Request two sets of structures. One with arginine at H40 and serine at L22. The other with
        alanine at H40 and threonine at L22 :
            ABangle -r H40 L22, H40 L22 -wa R S, A T
              or
            ABangle -r H40 L22 -wa R S, A T
        Use commas to separate sets of stuctures.

     4. Request one set of structures. Those with arginine OR alanine at H40 and serine OR threonine
        at L22:
            ABangle -r H40 L22 -wa R+A S+T
        Use '+' to signify 'or' logic.

     5. Request four sets of structures. Mouse Kappa structures, Mouse Lambda structures, Human Kappa
        structures and Human Lambda structures:
            ABangle -f Species Ltype -wp Mouse K, Mouse L, Human K, Human L

     6. Request 3 sets of structures. One with a HL angle within 2 degrees of -60 degrees; one 
        with HL angle greater than -50 degrees; one less than -65 degrees.
            ABangle -f HL -wp 2:-60, gt:-50, lt:-65
        For numerical factors use <option>:<x> , where <option> can be 'gt' (greater than), 'lt'
        (less than) or a number for 'within'. <x> is always a number.

     7. Request two sets of structures. One with Mouse Lambda structures with phenylalanine at L87 
        and LC1 within 2 degrees of 115 degrees; one with Unbound structures with an H3 loop length
        longer than 10 and with tryptophan at residue H50:
            ABangle -r L87, H50 -wa F, W -f Species Ltype LC1, Bstate H3length -wp Mouse L 2:115,
            Unbound gt:10
        Use commas to separate sets. Use the same order to specify your sets in -r -wa -f -wp args.

     8. Request sets of individual structures. One containing 12E8_HL and 1AY1_HL, one containing all
        of the user's structures (if stored, else all structures), one containing all fvs, and one
        containing all structures:
        from pdb 12E8:
            ABangle -s 12E8_HL 1AY1_HL, mine, 12E8, all
        Particular Fvs are labelled with PDBfile_HeavyChainLightChain. 

    9.  Find all the structures which have the same orientation as a target structure:
            ABangle -target 12E8_PM 


~ Visualisation of data.

    Optional Arguments:
    -showinfo           Show the information for each of the structures defined in the sets.
    -plot               Plot the distributions of the orientation measues. Use 'all' to plot all or
                        one of 'HL', 'HC1', 'HC2', 'LC1', 'LC2' or 'dc' to show one of the 
                        parameters.
    -lty                The type of line to draw for the sets. Choose from density plot 'd' or a
                        vertical line for each structrue in the set 'l'. Default is to use 'd' unless
                        the set size is too small.
    -bg                 Provide an alternative background distribution. Must be a .dat file in the 
                        format of the file found in abangle/data/Angles.dat.
    -png                Output plots as png image. Provide a filename with '.png' extension.
    -pymol              Show in PyMOL the sets of structures. Each are aligned (TMalign)to the light
                        chain consensus structure by default and are coloured according to set.
    -nalign             Define the maximum number of structures to show from each set.
    -useH               Align to the H chain consensus structure instead of the L chain.
    -showaxes           Show the coordinate system registered onto each of the structures in PyMOL.
    -msa                Show the msa of the structures selected.
    -mr                 Show the msa of the structures selected over certain residues.

    Examples:
     1. Plot angle distributions of sets: Mouse Kappa structures, Mouse Lambda structures, Human 
        Kappa structures and Human Lambda structures:
            ABangle -f Species Ltype -wp Mouse K, Mouse L, Human K, Human L -plot all
        show them in PyMOL:
            ABangle -f Species Ltype -wp Mouse K, Mouse L, Human K, Human L -pymol