Lilien Lab
Department of Computer Science
Centre for Cellular and Biomolecular Research
University of Toronto

Example scripts

A step-by-step tutorial is available but, if you'd prefer to get aligning as quickly as possible, download and run the following scripts to reproduce our heme and NAD experiments:

• Rigid heme alignment
• Rigid NAD alignment
• Flexible NAD alignment by nicotine moiety

Commands

• ligalign pivot-selection [, query-selection [, query-selection2, ...]]
  Computes a rigid alignment of the ligands in the query-selection(s) to the ligand in the pivot-selection. If no query-selection is specified, LigAlign will attempt to find appropriate ligands in a ligand similarity database, and display the bound proteins. If a specified PDB file is not found locally, LigAlign will automatically fetch the necessary files from the PDB. If there are multiple bound ligands in the proteins, LigAlign will choose the ligand from query-selection that is most similar to a ligand in the pivot-selection. LigAlign automatically reinitializes PyMOL on execution, as it needs clear caches to run correctly.
  


• ligalign_fragments pivot, query-selection [, query-selection2, ...]
  When the target's ligand is flexible, the best rigid alignment can still have bad overlap in the active sites. ligalign_fragments performs a substructure alignment of the ligands. It duplicates the target protein, aligning pieces of the fragment independently. The choice of best fragmentation is controlled by the ligalign_set settings. As with the ligalign command, if no query-selection is specified, LigAlign will attempt to find appropriate ligands automatically. This command generates a quantity of output as it enumerates alternative fragmentations; this output can be useful to track progress of the fragmentation process.
  


• ligalign_find_template diameter, percent-protein-representation, similarity, pivot [, query-selection, ...]
  Finds consistent clusters of residues in the protein active sites near the bound ligand. As well as providing a visualization, this command produces text output suitable for copy-and-paste into LaTex tables or ClustalW.
  
  ligalign_find_template will produce a "template" selection, comprising the clustered residues, and a "close_template" selection, which is the clustered residues within distant-residue-distance of the aligned ligand. The choice of distant-residue-distance is controlled by the ligalign_set settings and defaults to 4.5 angstroms. ligalign_find_template takes three parameters, in addition to the list of proteins to cluster:
  • diameter is the maximum diameter of the permitted clusters, in Angstroms.
  • representation is the minimum fraction of proteins that must be present in a cluster for it to be reported.
  • similarity imposes a requirement of chemical consistency on clusters. Similarity must be one of 'identity', 'chemical', or 'geometric'. The most conservative standard of chemical consistency is 'identity', which requires all residues in a cluster to be the same amino acid type. The similarity 'chemical' requires all residues in a cluster to be in the same chemical class: acidic (D, E), basic (R, H, K), amidic (N, Q), nonpolar (L, V, A, G, I, M, P), aromatic (F, W, Y), hydroxyl (S, R, Y), and sulphide bond forming (C). The most permissive standard of chemical consistency is 'geometric', which will report clusters consisting of any mix of amino acid types.
  
  


• ligalign_color_by_amino_acid_class selection
  Colors the residues in the selection according to their chemical class. The chemical classes and their corresponding colors are
  • acidic (D, E): pink
  • basic (R, H, K): blue
  • amidic (N, Q): green
  • nonpolar (L, V, A, G, I, M, P): orange
  • aromatic (F, W, Y): magenta
  • hydroxyl (S, R, Y): grey
  • sulphide bond forming (C): yellow
  Tyrosine is a member of two chemical groups but is always colored magenta.
  


• ligalign_reset_stored
  Clears LigAlign caches and calls PyMOL's reinitialize command.
  


• ligalign_color pivot-selection, query-selection
  Colors the residues in query-selection based on how far they are from the closest residue in pivot-selection. The center of each residue in the target selection is computed by averaging the location of each atom in the residue. This is repeated for the residues in the pivot selection. The minimum distance from each center in the target to any center in the pivot is computed and the target residue colored based on this minimum distance. Red means far (by default, more than 4.5 angstroms) and green means close (by default, less than 0.5 angstroms), with the distances in between discretized into ten groups, each with a color interpolated between red and green.
  


• ligalign_show_mapping query-selection
  Draw dashed lines showing the atom-to-atom mappings from query-selection to the pivot for which query-selection was aligned.
  


• ligalign_viz [setting=1-8] [, full_residues=True|False] [, entire_protein=True|False]
  A number of useful vizualizations of the region near the ligand. The default is setting 11.
  
  • setting 1 selects the atoms from any of the bound proteins which are near the ligands and shows them as spheres, using the default PyMOL coloration.
  • setting 2 shows the same nearby protein atoms as setting 1, but makes the atom spheres small, to less obscure the ligand alignment.
  • setting 3 takes the same atoms as settings 1 and 2 and computes an electrostatic surface over them, and displays this transparent closed consensus surface of the nearby atoms.
  • setting 4 shows the same consensus surface as setting 3, but makes it opaque.
  • setting 5 shows an open opaque consensus surface. This is the electrostatic surface where the edges of the active-site surface are computed to match the electrostatic surface of the rest of the protein, not just computed from the atoms near the ligands.
  • setting 6 shows the ligand as spheres and the active sites of any of the bound proteins as sticks.
  • setting 7 shows a closed surface which was computed independently over each query-selection.
  • setting 8 shows a closed surface and side-chains for each query-selection.
  • setting 9 shows side-chains for each query-selection.
  • setting 10 shows the atoms of the side-chains as a constellation of points.
  • setting 11 shows the aligned ligands.


• ligalign_set [cutoff | max_splits | min_fragment_size | distant_residue_distance], value
  Changes a number of ligalign parameters
  • cutoff is the %RMSD decrease below which we no longer try to increase the number of fragments (default: 0.1, i.e. 10%)
  • max_splits is the maximum number of fragments to permit (default: None, i.e. infinitely many)
  • min_fragment_size is the minimum number of atoms in a fragment (default: 4)
  • distant_residue_distance is the number of angstroms within which ligalign_find_template builds the "close_template" selection and beyond which ligalign_color will use bright red (default: 4.5)