Protein–Protein Interaction Maps
--------------------------------

Protein–protein interactions (PPI) modulate the function and activity of proteins in a 
variety of biological processes. Thus, understanding PPIs can facilitate the identification 
of targets for the development of both small-molecule and protein-based therapeutics. 
Protein–protein complex structures provide atomistic level insights into PPIs that drive 
complex formation, which can be used to guide protein engineering or the design of 
therapeutic molecules to enhance or diminish specific PPI for a desired pharmacological 
outcome. SilcsBio provides a utility to study PPIs through the command line interface, 
SILCS-PPI. SILCS-PPI uses SILCS FragMaps to efficiently guide fast Fourier transform 
(FFT)-based protein docking. The resulting SILCS-PPI docking provides probability 
distributions of PPI interactions over the surface of both partner proteins, allowing 
for the identification of alternate binding poses. The SILCS-PPI utility can 
additionally be used to build PDB structures of protein–protein complexes encompasing 
these alternate binding poses. Details on SILCS-PPI are provided in ref :cite:`Yu:2019`. 
The procedure for performing SILCS-PPI on two partner proteins is provided below:

1. Set up and run SILCS-PPI calculations:

   ::

        $SILCSBIODIR/ppi/1_setup_ppi prot1=<first prot pdb> mapsdir1=<location and 
        name of directory containing FragMaps> prot2=<second prot pdb> mapsdir2=<location 
        and name of directory containing FragMaps>

   The command for setting up and running SILCS-PPI calculations requires precomputed FragMaps 
   of the two proteins of interest. If self-interactions are of interest, as in the case of protein 
   aggregation, then the same input 
   should be provided for ``prot1`` and ``prot2`` as well as ``mapsdir1`` and ``mapsdir2``.

   *Required parameters*:

   * Path and name of first input protein PDB file (receptor protein):

      ::

          prot1=<first prot pdb>

   * Path and name of FragMaps for first input protein (receptor protein):

      ::

          mapsdir1=<location and name of directory containing FragMaps for first protein>

   * Path and name of second input protein PDB file (ligand protein):

      ::

          prot2=<second prot pdb>

   * Path and name of FragMaps for second input protein (ligand protein):

      ::

          mapsdir2=<location and name of directory containing FragMaps for second protein>

   *Optional parameters*:

   * Option to use the full FragMap of protein 1 (receptor protein):

      ::
            
          fullmap=<true/false; flag for using full map or not. default=true>

     The SILCS-PPI calculation can be focused on a portion of the receptor protein. 
     When ``fullmap=false``, the ``center`` and ``radius`` parameters must be set.

   * Rotation step size:

      ::

          rotsize=<rotation step size; default=15 degrees>

   * Number of solutions saved per rotation:

      ::

          numsol=<# of solution per rotation; default=1>

   * Center for transformation:
  
      ::

          center=<"x,y,z"; e.g. center="20,30,-2">

     The ``center`` parameter defines the center of the protein–protein contact region on 
     the receptor protein. The ``center`` parameter must be used with the ``radius`` 
     parameter when ``fullmap=false``.

   * Radius for transformation:

      ::

          radius=<integer value>
    
     The ``radius`` parameter defines the radius of the protein–protein contact region 
     on the receptor protein. All solutions will be restricted to be within the radius 
     from the specified center. The ``radius`` parameter must be used with the ``center`` 
     parameter when ``fullmap=false``.

   * Option to bundle jobs:
  
      ::

          bundle=<true/false; default=false>

   * Number of jobs to bundle into one larger job:

      ::

          njobs=<# of jobs used when bundle=true; default=16> 

   * Option to filter energy grids:

      ::  
            
          filter=<true/false; default=true>

     By default, energy grids are filtered prior to SILCS-PPI calculations to remove 
     unnecessary information. In the FragMaps, all voxels that are 
     5 Å away from the excluded area (defined by exclusion maps) are removed as those 
     grids correspond to bulk phase behavior of the solutes rather than binding 
     patterns on the protein surface. In the protein probability grids (PPGs), all 
     voxels that are overlapping with the excusion map are removed as they represent 
     the repulsive core of the protein.

2. Collect SILCS-PPI results:

   ::

       $SILCSBIODIR/ppi/2_collect_ppi prot1=<first prot pdb> prot2=<second prot pdb>

   *Required parameters*:

   * Path and name of first input protein PDB file (receptor protein):

      ::

          prot1=<first prot pdb>

   * Path and name of second input protein PDB file (ligand protein):

      ::

          prot2=<second prot pdb>
    
     .. note::

       The entries for ``prot1`` and ``prot2`` must be the same as those used in the 
       first step, ``1_setup_ppi``.
    
   *Optional parameters*:

   * Path and name of SILCS-PPI results:

      :: 
            
          ppidir=<folder where PPI result is stored; default: 3_ppi>
    
   * Option to cluster results:

      ::

          cluster=<perform clustering; default=true>
  
   * Number of clusters to output:
    
      ::
            
          topn=<number of top cluster to output; default=2000>

3. Build protein–protein complex structures in PDB format:

   ::

       $SILCSBIODIR/ppi/3_build_cmpx_pdb prot1=<receptor prot pdb> prot2=<ligand prot pdb> 
       logfile=<PPI logfile> prefix=<prefix for output>

   *Required parameters*:

   * Path and name of first input protein PDB file (receptor protein):

      ::

          prot1=<first prot pdb>

   * Path and name of second input protein PDB file (ligand protein):

      ::

          prot2=<second prot pdb>
    
     .. note::

       The entry for ``prot1`` and ``prot2`` must be the same as those used in the 
       first step, ``1_setup_ppi``.
    
   * Path and name of SILCS-PPI log file:

      :: 

          logfile=<PPI logfile>
    
   * Prefix for output PDB file names:

      ::

          prefix=<prefix for output>