extract_motifs.cc

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// -*- mode:c++;tab-width:2;indent-tabs-mode:t;show-trailing-whitespace:t;rm-trailing-spaces:t -*-
// vi: set ts=2 noet:
//
// (c) Copyright Rosetta Commons Member Institutions.
// (c) This file is part of the Rosetta software suite and is made available under license.
// (c) The Rosetta software is developed by the contributing members of the Rosetta Commons.
// (c) For more information, see http://www.rosettacommons.org. Questions about this can be
// (c) addressed to University of Washington UW TechTransfer, email: license@u.washington.edu.

/// @file
/// @brief Application to extract motifs from a set of pdb files

// libRosetta headers

#include <core/types.hh>

#include <core/conformation/Conformation.hh>
#include <core/pose/Pose.hh>
#include <core/pose/PDBInfo.hh>
#include <core/scoring/ScoreFunction.hh>
#include <core/import_pose/import_pose.hh>
#include <core/io/pdb/pose_io.hh>

#include <basic/options/util.hh>
#include <basic/options/option.hh>
#include <basic/options/keys/in.OptionKeys.gen.hh>
#include <basic/options/keys/out.OptionKeys.gen.hh>
#include <basic/options/keys/motifs.OptionKeys.gen.hh>

#include <basic/basic.hh>
#include <basic/Tracer.hh>

#include <protocols/motifs/Motif.hh>
#include <protocols/motifs/SingleMotif.hh>
#include <protocols/motifs/MotifLibrary.hh>

// C++ headers
#include <fstream>
//silly using/typedef


//utilities
#include <protocols/jd2/JobDistributor.hh>
#include <devel/init.hh>
#include <utility/excn/Exceptions.hh>

//using namespace basic;
using namespace core;
using namespace pose;
using namespace chemical;
using namespace scoring;
using namespace ObjexxFCL;
using namespace basic::options;
using namespace basic::options::OptionKeys;


// These are for aligning all interactions to a common coordinate frame.
// They don't need to be realistic

Vector const atom1_vector(   1.500,  0.000,  0.000 );
Vector const atom2_vector(   0.000,  0.000,  0.000 );
Vector const atom3_vector(   0.000,  1.500,  0.000 );

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///////////////////////////////////////////////////////////////////////////////

static THREAD_LOCAL basic::Tracer TR( "extract_motifs" );

void
fetch_atom_names(
  core::chemical::AA const & aa,
  std::string & oa1,
  std::string & oa2,
  std::string & oa3
)
{
  switch( aa ) {
  case aa_ala :
    oa1 = "1HB";
    oa2 = "CB";
    oa3 = "2HB";
    break;
  case aa_cys :
    oa1 = "SG";
    oa2 = "CB";
    oa3 = "CA";
    break;
  case aa_asp :
    oa1 = "OD1";
    oa2 = "CG";
    oa3 = "OD2";
    break;
  case aa_glu :
    oa1 = "OE1";
    oa2 = "CD";
    oa3 = "OE2";
    break;
  case aa_phe :
    oa1 = "CG";
    oa2 = "CD1";
    oa3 = "CZ";
    break;
  case aa_gly :
    oa1 = "HA1";
    oa2 = "CA";
    oa3 = "HA2";
    break;
  case aa_his :
    oa1 = "ND1";
    oa2 = "CE1";
    oa3 = "NE2";
    break;
  case aa_ile :
    oa1 = "CD1";
    oa2 = "CG1";
    oa3 = "CB";
    break;
  case aa_lys :
    oa1 = "NZ";
    oa2 = "CE";
    oa3 = "CD";
    break;
  case aa_leu :
    oa1 = "CD1";
    oa2 = "CG";
    oa3 = "CD2";
    break;
  case aa_met :
    oa1 = "CG";
    oa2 = "SD";
    oa3 = "CE";
    break;
  case aa_asn :
    oa1 = "OD1";
    oa2 = "CG";
    oa3 = "ND2";
    break;
  case aa_gln :
    oa1 = "OE1";
    oa2 = "CD";
    oa3 = "NE2";
    break;
  case aa_arg :
    oa1 = "NH1";
    oa2 = "CZ";
    oa3 = "NH2";
    break;
  case aa_ser :
    oa1 = "HG";
    oa2 = "OG";
    oa3 = "CB";
    break;
  case aa_thr :
    oa1 = "HG1";
    oa2 = "OG1";
    oa3 = "CB";
    break;
  case aa_val :
    oa1 = "CG1";
    oa2 = "CB";
    oa3 = "CG2";
    break;
  case aa_trp :
    oa1 = "CG";
    oa2 = "CE2";
    oa3 = "CZ3";
    break;
  case aa_tyr :
    oa1 = "CG";
    oa2 = "CD1";
    oa3 = "CZ";
    break;
  default :
    TR << "Did not find residue type for " << name_from_aa( aa ) << std::endl;
    oa1 = "X";
    oa2 = "X";
    oa3 = "X";
  }

  return;
}

void
output_single_motif(
  Pose & src_pose,
  AA const & target_aa,
  std::string & pdb_name,
  int prot_pos,
  std::vector< Size > &  contacts
)
{

  // Make a temporary pose
  Pose pose;

  // These need to be assigned be looking at the target amino acid
  std::string atom1_name;
  std::string atom2_name;
  std::string atom3_name;
  fetch_atom_names( target_aa, atom1_name, atom2_name, atom3_name );

  pose.append_residue_by_jump( src_pose.residue( prot_pos ), 1 );
  for ( Size ic = 0 ; ic < contacts.size() ; ++ic ) {
    Size dna_pos = contacts[ ic ];
    pose.append_residue_by_jump( src_pose.residue( dna_pos ), 1 );
  }
  pose.conformation().insert_chain_ending( 1 );

  // Make a second pose _just for orientation_

  Pose centered_pose;
  centered_pose = pose;

  // Fix key residues
  centered_pose.set_xyz( id::AtomID( centered_pose.residue( 1 ).atom_index( atom1_name ), 1 ), atom1_vector );
  centered_pose.set_xyz( id::AtomID( centered_pose.residue( 1 ).atom_index( atom2_name ), 1 ), atom2_vector );
  centered_pose.set_xyz( id::AtomID( centered_pose.residue( 1 ).atom_index( atom3_name ), 1 ), atom3_vector );

  // Move the pose onto this fixed point

  core::kinematics::Stub end_stub(
    centered_pose.residue( 1 ).atom( atom2_name ).xyz(),
    centered_pose.residue( 1 ).atom( atom1_name ).xyz(),
    centered_pose.residue( 1 ).atom( atom2_name ).xyz(),
    centered_pose.residue( 1 ).atom( atom3_name ).xyz()
  );

  core::kinematics::Stub start_stub(
    pose.residue( 1 ).atom( atom2_name ).xyz(),
    pose.residue( 1 ).atom( atom1_name ).xyz(),
    pose.residue( 1 ).atom( atom2_name ).xyz(),
    pose.residue( 1 ).atom( atom3_name ).xyz()
  );

  for ( Size ires = 1 ; ires <= pose.total_residue() ; ++ires ) {
    for ( Size iatom = 1 ; iatom <= pose.residue(ires).natoms() ; ++iatom ) {
      pose.set_xyz( id::AtomID( iatom, ires ),
        end_stub.local2global( start_stub.global2local( pose.residue(ires).xyz( iatom ) ) ) );
    }
  }

  std::string const output_path( option[ out::path::pdb ]() );
  std::string delimiter( "_" );
  //std::string extension( ".pdb" );
  std::string motif_file_name( output_path + src_pose.residue_type( prot_pos ).name3() +
    string_of( src_pose.pdb_info()->number( prot_pos ) ) +
    string_of( src_pose.pdb_info()->chain( prot_pos ) ) + delimiter );

  for ( Size ic = 0 ; ic < contacts.size() ; ++ic ) {
    Size dna_pos = contacts[ ic ];
    motif_file_name = motif_file_name +
      src_pose.residue_type( dna_pos ).name1() +
      string_of( src_pose.pdb_info()->number( dna_pos ) ) +
      string_of( src_pose.pdb_info()->chain( dna_pos ) ) + delimiter;
  }

  //motif_file_name = motif_file_name + pdb_name + extension;
  motif_file_name = motif_file_name + pdb_name;

  TR << "Writing " << motif_file_name << std::endl;
  io::pdb::dump_pdb( pose, motif_file_name );

}

void
motif_distances
(
  protocols::motifs::Motif const & m1,
  protocols::motifs::Motif const & m2,
  core::Real & dist_diff,
  core::Real & angl_diff

)
{

  // Handle when motifs have different residue pairs
  if ( m1.restype_name1() != m2.restype_name1() ||
      m1.restype_name2() != m2.restype_name2() ) {
    dist_diff = angl_diff = 9999.0;
    return;
  }

  core::kinematics::jump_distance( m1.forward_jump(), m2.forward_jump(), dist_diff, angl_diff );

  return;
}


///////////////////////////////////////////////////////////////////////////////
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Real
get_packing_score(
  Pose & pose,
  Size pos1,
  Size pos2,
  ScoreFunction & sf
)
{

  EnergyMap pack_map;

  sf.eval_ci_2b_sc_sc( pose.residue( pos1 ), pose.residue( pos2 ), pose, pack_map );

  return pack_map[ fa_atr ] + pack_map[ fa_rep ];
}

Real
get_hbond_score(
  Pose & pose,
  Size pos1,
  Size pos2,
  ScoreFunction & sf
)
{

  EnergyMap hbond_map;

  sf.eval_cd_2b_sc_sc( pose.residue( pos1 ), pose.residue( pos2 ), pose, hbond_map );

  return hbond_map[ hbond_sc ];
}

Real
get_elec_score(
  Pose & pose,
  Size pos1,
  Size pos2,
  ScoreFunction & sf
)
{

  EnergyMap elec_map;

  sf.eval_cd_2b_sc_sc( pose.residue( pos1 ), pose.residue( pos2 ), pose, elec_map );

  return elec_map[ fa_elec ];

}

///////////////////////////////////////////////////////////////////////////////
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///////////////////////////////////////////////////////////////////////////////

void
process_for_motifs(
  Pose & pose,
  std::string & pdb_name,
  chemical::AA const target_aa,
  protocols::motifs::MotifLibrary & motif_lib
)
{
  int nres( pose.total_residue() );

  Real dist_threshold( option[ motifs::duplicate_dist_cutoff ]  );
  Real angl_threshold( option[ motifs::duplicate_angle_cutoff ] );

  Real pack_min_threshold( option[ motifs::pack_min_threshold ] );
  Real pack_max_threshold( option[ motifs::pack_max_threshold ] );
  Real hbond_min_threshold( option[ motifs::hbond_min_threshold ] );
  Real hbond_max_threshold( option[ motifs::hbond_max_threshold ] );
  Real elec_min_threshold( option[ motifs::elec_min_threshold ] );
  Real elec_max_threshold( option[ motifs::elec_max_threshold ] );

  // Get a simple scorefunction to screen for thresholds
  ScoreFunction scorefxn;
  // These are talaris2013 values.  Since the thresholds can be
  // chosen arbitrarily, the only thing that is truly hard-wired
  // here is the ratio between fa_atr and fa_rep, which are
  // combined in get_packing_score above.
  scorefxn.set_weight( fa_atr, 0.8 );
  scorefxn.set_weight( fa_rep, 0.44 );
  scorefxn.set_weight( hbond_sc, 1.1 );
  scorefxn.set_weight( fa_elec, 0.7 );
  scorefxn.setup_for_scoring( pose );

  // These need to be assigned be looking at the target amino acid
  std::string atom1_name;
  std::string atom2_name;
  std::string atom3_name;
  fetch_atom_names( target_aa, atom1_name, atom2_name, atom3_name );

  // Loop over positions, skipping things that aren't the target amino acid
  for ( int aaoi_pos = 1 ; aaoi_pos <= nres ; ++aaoi_pos ) {
    ResidueType const & res_type( pose.residue_type( aaoi_pos ) );

    if ( res_type.aa() != target_aa ) continue;

    std::vector< Size > contacts;

    Real total_pack_score( 0.0 );
    Real total_hb_score( 0.0 );
    Real check_hb_score( 0.0 );

    // Loop over all other positions
    for ( int other_pos = 1 ; other_pos <= nres ; ++other_pos ) {
      ResidueType const & other_type( pose.residue_type( other_pos ) );
      if ( other_pos == aaoi_pos ) continue;

      // This prevents against getting the same interaction twice
      if ( ( other_type.aa() == target_aa ) && ( other_pos < aaoi_pos ) ) continue;

      Real pack_score = get_packing_score( pose, other_pos, aaoi_pos, scorefxn );
      Real hb_score = get_hbond_score( pose, other_pos, aaoi_pos, scorefxn );
      Real elec_score = get_elec_score( pose, other_pos, aaoi_pos, scorefxn );

      int num_contacts( 0 );

      // Loop over all amino acid atoms
      for ( Size this_atom = 1 ; this_atom <= res_type.nheavyatoms() ; ++this_atom ) {
        // Loop over heavy atoms
        for ( Size other_atom = other_type.first_sidechain_atom() ;
            other_atom <= other_type.nheavyatoms() ; ++other_atom ) {

          Real const dis2( pose.residue( other_pos ).xyz( other_atom ).distance_squared(
            pose.residue( aaoi_pos ).xyz( this_atom ) ) );
          if ( dis2 < (3.9*3.9) ) {
            ++num_contacts;
          }

        }
      } // End loop over atoms

      check_hb_score += hb_score;

      //   if( num_contacts > 0 )
      //   if( pack_score <= -0.5 && hb_score > -0.2 )
      //   if( hb_score <= -1.00 ) {
      //   if( pack_score <= -1.00 ) {

      if ( ( pack_score > pack_min_threshold && pack_score < pack_max_threshold) &&
          ( hb_score > hbond_min_threshold && hb_score < hbond_max_threshold) &&
          ( elec_score > elec_min_threshold && elec_score < elec_max_threshold) ) {

        TR << "Energies between " << aaoi_pos << " and " << other_pos << " are pack: " << pack_score << " hbond: " << hb_score << std::endl;

        total_pack_score += pack_score;
        total_hb_score += hb_score;

        // Store the motif info
        std::string other_atom1;
        std::string other_atom2;
        std::string other_atom3;
        fetch_atom_names( pose.aa( other_pos ), other_atom1, other_atom2, other_atom3 );
        if ( other_atom1 != "X" ) {
          contacts.push_back( other_pos );
          protocols::motifs::SingleMotif new_motif( pose, aaoi_pos, atom1_name, atom2_name, atom3_name, other_pos, other_atom1, other_atom2, other_atom3 );
          std::string motif_origin( pose.residue_type( aaoi_pos ).name3() + " " + string_of( pose.pdb_info()->number( aaoi_pos ) ) + string_of( pose.pdb_info()->chain( aaoi_pos ) ) + " and " + pose.residue_type( other_pos ).name3() + " " + string_of( pose.pdb_info()->number( other_pos ) ) + string_of( pose.pdb_info()->chain( other_pos ) ) + " pdb code:  " + pdb_name );
          new_motif.store_remark( motif_origin );
          TR << new_motif.remark() << std::endl;

          protocols::motifs::Motif work_motif( new_motif );

          bool unique_motif( true );

          // Check against other motifs
          core::Size check_i( 1 );
          for ( protocols::motifs::MotifCOPs::const_iterator this_motif = motif_lib.begin() ; this_motif != motif_lib.end() ; ++this_motif ) {
            core::Real dist_diff( 0.0 );
            core::Real angl_diff( 0.0 );
            motif_distances( work_motif, **this_motif, dist_diff, angl_diff );
            //      TR << "Motif dist from current motif " << check_i << " is translation " << dist_diff << " and angle " << angl_diff << std::endl;
            check_i++;
            if ( dist_diff < dist_threshold && angl_diff < angl_threshold ) {
              unique_motif = false;
              break;
            }
          }

          if ( unique_motif ) {
            motif_lib.add_to_library( new_motif );
          }
        }
      }

    } // End loop over amino acids

    if ( contacts.size() > 0 ) {
      TR << "Outputing motif with " << contacts.size() << " contacts " << std::endl;
      TR << "Energies are pack: " << total_pack_score << " hbond: " << total_hb_score << std::endl;
      TR << "Check HB Energy is: " << check_hb_score << std::endl;
      output_single_motif( pose, target_aa, pdb_name, aaoi_pos, contacts );
    }


  } // End loop over residues

  return;
}


///////////////////////////////////////////////////////////////////////////////
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///////////////////////////////////////////////////////////////////////////////

int
main( int argc, char * argv [] )
{
  try {
    using namespace pose;
    using namespace conformation;
    using namespace chemical;
    using namespace import_pose;

    //using namespace core;
    devel::init( argc, argv );

    // Get the name of the file that contains the pdb files for extraction
    std::string const list_of_pdb_files( option[ in::file::l ]()[1] );
    std::ifstream file_data( list_of_pdb_files.c_str() );

    // find the amino acid for which interaction motifs are requested
    std::string target_3code( option[ motifs::target_aa ]() );
    chemical::AA target_aa( aa_from_name( uppercase( target_3code ) ) );

    std::string pdb_code;

    protocols::motifs::MotifLibrary motif_lib;

    std::string const output_path( option[ out::path::pdb ]() );
    std::string motif_path_and_file( output_path + "motif_library" );
    std::ofstream motif_ostream( motif_path_and_file.c_str() );

    file_data >> pdb_code;
    while ( !file_data.eof() ) {

      TR << "Working on pdb " << pdb_code << std::endl;
      std::string const pdb_file_path( option[ in::path::pdb ]( 1 ) );
      std::string pdb_file( pdb_file_path + pdb_code );
      TR << "PDB file " << pdb_file << std::endl;

      Pose pose;
      pose_from_pdb( pose, pdb_file );

      process_for_motifs( pose, pdb_code, target_aa, motif_lib );

      file_data >> pdb_code;
    }

    motif_ostream << motif_lib;
    motif_ostream.close();

    return 0;
  } catch ( utility::excn::EXCN_Base const & e ) {
    std::cout << "caught exception" << e.msg() << std::endl;
    return -1;
  }
}

///////////////////////////////////////////////////////////////////////////////