EnzdesFixBBProtocol.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   protocols/enzdes/EnzdesFixBBProtocol.cc
///
/// @brief
/// @author Florian Richter


#include <protocols/enzdes/EnzdesFixBBProtocol.hh>
#include <protocols/enzdes/EnzdesBaseProtocol.hh>
// AUTO-REMOVED #include <protocols/toolbox/match_enzdes_util/EnzConstraintIO.hh>
#include <protocols/enzdes/EnzdesMovers.hh>
#include <protocols/enzdes/ModifyStoredLigandRBConfsMovers.hh>
// AUTO-REMOVED #include <core/chemical/ResidueType.hh>
#include <basic/options/option.hh>
#include <core/pack/task/PackerTask.hh>
#include <core/pose/Pose.hh>
#include <core/scoring/ScoreFunction.hh>
#include <protocols/ligand_docking/LigandDockProtocol.hh>
// AUTO-REMOVED #include <protocols/moves/MonteCarlo.hh>
#include <protocols/simple_moves/PackRotamersMover.hh>
#include <protocols/simple_moves/ConsensusDesignMover.hh>

#include <basic/Tracer.hh>

// option key includes

#include <basic/options/keys/enzdes.OptionKeys.gen.hh>
#include <basic/options/keys/in.OptionKeys.gen.hh>
#include <utility/vector0.hh>
#include <utility/vector1.hh>

namespace protocols{
namespace enzdes{

static basic::Tracer tr("protocols.enzdes.EnzdesFixBBProtocol");

EnzdesFixBBProtocol::EnzdesFixBBProtocol()
  : EnzdesBaseProtocol(),
    start_from_random_rb_conf_( basic::options::option[basic::options::OptionKeys::enzdes::start_from_random_rb_conf] )
{}

EnzdesFixBBProtocol::~EnzdesFixBBProtocol(){}

void
EnzdesFixBBProtocol::apply(
  core::pose::Pose & pose
){


  using namespace protocols::moves;
  using namespace core::pack::task;

  // Scoring function already set up by superclass
  tr.Info << "starting apply function..." << std::endl;

  //set the native pose if requested
  if( ! basic::options::option[basic::options::OptionKeys::in::file::native].user() ){

    core::pose::PoseOP natpose = new core::pose::Pose( pose );
    (*scorefxn_)( *natpose );
    this->set_native_pose( natpose );
  }

  //set up constraints (read cstfile, do mapping, etc, then add to pose)
  if( basic::options::option[basic::options::OptionKeys::enzdes::cstfile].user() ){
    enable_constraint_scoreterms();
    setup_enzdes_constraints( pose, false );
  }

  if( start_from_random_rb_conf_ ){
    ApplyRandomStoredRBConf ranconf;
    ranconf.apply( pose );
  }

  //create packer task (read resfile, etc)
  PackerTaskOP design_pack_task;

  tr.Info << "Done setting up the task and constraints... " << std::endl;
  //score pose to make sure everything is initialised correctly
  (*scorefxn_)( pose );

  //cst opt stage, if demanded
  if(basic::options::option[basic::options::OptionKeys::enzdes::cst_opt]){
    design_pack_task =  create_enzdes_pack_task( pose );
    tr.Info << "starting cst_opt minimization..." << std::endl;
    cst_minimize(pose, design_pack_task, true);
    (*scorefxn_)( pose );
    tr.Info << "done cst_opt minimization." << std::endl;
  }


  if(basic::options::option[basic::options::OptionKeys::enzdes::cst_predock])
  {
    //design_pack_task =  create_enzdes_pack_task( pose );
    PredesignPerturbMoverOP predock = new PredesignPerturbMover();
    predock->set_ligand( get_ligand_id(pose, pose.num_jump()) );
    predock->apply(pose);
    (*scorefxn_)( pose );
  }


  if(basic::options::option[basic::options::OptionKeys::enzdes::cst_design]){

    design_pack_task = create_enzdes_pack_task( pose ); //make a new task in case the ligand has moved a lot
    tr.Info << "starting cst_design, " << basic::options::option[basic::options::OptionKeys::enzdes::design_min_cycles] << " cycles of design/minimization ... " << std::endl;

    core::Size design_min_cycles = basic::options::option[basic::options::OptionKeys::enzdes::design_min_cycles];

//    bool favor_native_res(false);
//    if( basic::options::option[basic::options::OptionKeys::enzdes::favor_native_res].user() ) favor_native_res = true;

    enzdes_pack( pose, design_pack_task, scorefxn_, design_min_cycles, basic::options::option[basic::options::OptionKeys::enzdes::cst_min], false, true );

    design_pack_task = create_enzdes_pack_task( pose, false );

    if( basic::options::option[basic::options::OptionKeys::enzdes::cst_min] ){
      remove_enzdes_constraints( pose, true );
      cst_minimize(pose, design_pack_task);
      add_pregenerated_enzdes_constraints( pose );
    }
    (*scorefxn_)( pose );

  } //if cst_design

  else if( basic::options::option[basic::options::OptionKeys::enzdes::cst_min] ){

    design_pack_task = create_enzdes_pack_task( pose );

    cst_minimize(pose, design_pack_task);

    (*scorefxn_)( pose );
  }

  if( basic::options::option[basic::options::OptionKeys::enzdes::make_consensus_mutations] ){

    simple_moves::ConsensusDesignMover consensus_mover( create_enzdes_pack_task( pose, false ), scorefxn_ );
    consensus_mover.set_invert_task( true );
    consensus_mover.set_use_seqprof_constraints( true );
    consensus_mover.set_sasa_cutoff( 1.0 ); //let's prevent totally buried residues from being redesigned
    consensus_mover.apply( pose );
  }

  PackerTaskOP repack_task;


  //do a repack without constraints
  if( ! basic::options::option[basic::options::OptionKeys::enzdes::no_unconstrained_repack]){

    remove_enzdes_constraints( pose, true );
    (*scorefxn_)( pose );
    repack_task = create_enzdes_pack_task( pose, false ); //remake task in case the ligand has moved a lot
    tr.Info << "Starting after design unconstrained repack/minimization... " << std::endl;
    protocols::simple_moves::PackRotamersMoverOP enzdes_repack = new protocols::simple_moves::PackRotamersMover(scorefxn_, repack_task);
    enzdes_repack->apply( pose );

    if(basic::options::option[basic::options::OptionKeys::enzdes::cst_min]) cst_minimize(pose, repack_task);

    //and turn constraints back on for the final scoring
    add_pregenerated_enzdes_constraints( pose );
    tr.Info <<"Finished after design unconstrained repack/minimization... " << std::endl;

    (*scorefxn_)( pose );

  }

  if(basic::options::option[basic::options::OptionKeys::enzdes::cst_dock] ){


    //note: this is not really ready to go yet, still to be developed
    //to do: write a wrapper that executes the docking protocol a number
    //of times, either till a maximum number of decoys is produced, or
    //until a decoy is found that has a better energy than the designed pose

    tr.Info << "Starting ligand docking... " << std::endl;
    remove_enzdes_constraints( pose, false );
    //write stuff for ligand docking protocol
    protocols::ligand_docking::LigandDockProtocolOP dock_lig_protocol = new protocols::ligand_docking::LigandDockProtocol();
    dock_lig_protocol->apply( pose );

    add_pregenerated_enzdes_constraints( pose );
    (*scorefxn_)( pose );

  }


} //apply function


std::string
EnzdesFixBBProtocol::get_name() const {
  return "EnzdesFixBBProtocol";
}

void
EnzdesFixBBProtocol::register_options()
{
  using namespace basic::options;

  option.add_relevant( OptionKeys::enzdes::cstfile );
  option.add_relevant( OptionKeys::enzdes::cst_opt );
  option.add_relevant( OptionKeys::enzdes::cst_predock );

  PredesignPerturbMover::register_options();

  option.add_relevant( OptionKeys::enzdes::cst_design );
  option.add_relevant( OptionKeys::enzdes::design_min_cycles );
  option.add_relevant( OptionKeys::enzdes::no_unconstrained_repack );

  option.add_relevant( OptionKeys::in::file::pssm);
}

} //namespace enzdes
} //namespace protocols