This notebook contains material from PyRosetta; content is available on Github.

Ligand Refinement in PyRosetta (a.k.a. High-Resolution Local Docking) Using the ligand.wts Scorefunction

Warning: This notebook uses pyrosetta.distributed.viewer code, which runs in jupyter notebook and might not run if you're using jupyterlab.

In [1]:
# Notebook setup
import sys
if 'google.colab' in sys.modules:
    !pip install pyrosettacolabsetup
    import pyrosettacolabsetup
    pyrosettacolabsetup.mount_pyrosetta_install()
    print ("Notebook is set for PyRosetta use in Colab.  Have fun!") 
    
import logging
logging.basicConfig(level=logging.INFO)
import os
import pyrosetta
import pyrosetta.distributed
import pyrosetta.distributed.viewer as viewer

Initialize PyRosetta and setup the input pose:

In [2]:
params_file = "inputs/TPA.gasteiger.fa.params"
flags = f"""
-extra_res_fa {params_file} # Provide a custom TPA .params file
-ignore_unrecognized_res 1
-mute all
"""
pyrosetta.distributed.init(flags)
pose = pyrosetta.io.pose_from_file("inputs/test_lig.pdb")
INFO:pyrosetta.distributed:maybe_init performing pyrosetta initialization: {'extra_options': '-extra_res_fa inputs/TPA.gasteiger.fa.params -ignore_unrecognized_res 1 -mute all', 'silent': True}
INFO:pyrosetta.rosetta:Found rosetta database at: /mnt/home/klimaj/git/Rosetta/main/source/src/python/PyRosetta/src/pyrosetta/database; using it....
INFO:pyrosetta.rosetta:PyRosetta-4 2019 [Rosetta PyRosetta4.conda.linux.CentOS.python36.Release 2019.39+release.93456a567a8125cafdf7f8cb44400bc20b570d81 2019-09-26T14:24:44] retrieved from: http://www.pyrosetta.org
(C) Copyright Rosetta Commons Member Institutions. Created in JHU by Sergey Lyskov and PyRosetta Team.

Before we perform ligand refinement, let's take a look at the input .pdb file using the pyrosetta.distributed.viewer macromolecular visualizer:

In [8]:
chE = pyrosetta.rosetta.core.select.residue_selector.ChainSelector("E")

view = viewer.init(pose)
view.add(viewer.setStyle())
view.add(viewer.setStyle(command=({"hetflag": True}, {"stick": {"colorscheme": "brownCarbon", "radius": 0.2}})))
view.add(viewer.setSurface(residue_selector=chE, opacity=0.7, color='white'))
view.add(viewer.setHydrogenBonds())
view()

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
jupyter labextension install jupyterlab_3dmol


Restart Jupyter Notebook kernel to properly re-initialize PyRosetta


In [1]:
# Notebook setup
import sys
if 'google.colab' in sys.modules:
    !pip install pyrosettacolabsetup
    import pyrosettacolabsetup
    pyrosettacolabsetup.mount_pyrosetta_install()
    print ("Notebook is set for PyRosetta use in Colab.  Have fun!") 
    
import logging
logging.basicConfig(level=logging.INFO)
import os
import pyrosetta
import pyrosetta.distributed
import pyrosetta.distributed.viewer as viewer

The following ligand refinement example was adapted from ~Rosetta/main/source/src/python/PyRosetta/src/demo/D120_Ligand_interface.py:

In [9]:
def sample_ligand_interface(pdb_filename,
                            partners,
                            ligand_params=[""],
                            jobs=1,
                            job_output="ligand_output"):
    """
    Performs ligand-protein docking using Rosetta fullatom docking
    (DockingHighRes) on the ligand-protein complex in  <pdb_filename>
    using the relative chain  <partners>. If the ligand parameters
    (a .params file) are not defaultly loaded into PyRosetta,
    <ligand_params> must supply the list of files including the ligand
    parameters. <jobs>  trajectories are performed with output
    structures named <job_output>_(job#).pdb.
    
    Note: Global docking, a problem solved by the Rosetta DockingProtocol,
    requires interface detection and refinement as with other protocols,
    these tasks are split into centroid (interface detection) and
    high-resolution (interface refinement) methods without a centroid 
    representation, low-resolution ligand-protein prediction is not
    possible and as such, only the high-resolution ligand-protein 
    interface refinement is available. If you add a perturbation or 
    randomization step, the high-resolution stages may fail. A perturbation
    step CAN make this a global docking algorithm however the rigid-body
    sampling preceding refinement requires extensive sampling to produce
    accurate results and this algorithm spends most of its effort in
    refinement (which may be useless for the predicted interface).
    
    This script performs ligand-protein interface structure prediction but does NOT
    perform global ligand-protein docking. Since there is no generic interface
    detection, the input PDB file must have the ligand placed near the interface
    that will be refined. If the DockMCMProtocol is applied to a pose
    without placement near the interface, then the refinement may:
        -waste steps sampling the wrong interface
        -fail by predicting an incorrect interface very far from the true interface
        -fail by separating the ligand from the protein (usually due to a clash)
    DockMCMProtocol does not require an independent randomization or perturbation
    step to "seed" its prediction.
    
    Additional refinement steps may increase the accuracy of the predicted
    conformation (see refinement.py). Drastic moves (large conformational changes)
    should be avoided; if they precede the protocol, the problems above may occur,
    if they succeed the protocol, the protocol results may be lost.
    """

    # Declare working directory and output directory
    working_dir = os.getcwd()
    output_dir = "outputs"
    if not os.path.exists(output_dir):
        os.mkdir(output_dir)
    
    # Initialize PyRosetta
    pyrosetta.init()
    
    # Create an empty pose from the desired PDB file
    pose = pyrosetta.rosetta.core.pose.Pose()

    # If the params list has contents, load .params files
    # Note: this method of adding ligands to the ResidueTypeSet is unnecessary
    # if you call pyrosetta.init("-extra_res_fa {}".format(ligand_params))
    if len(ligand_params) != 0 and ligand_params[0] != "":
        ligand_params = pyrosetta.Vector1(ligand_params)
        res_set = pose.conformation().modifiable_residue_type_set_for_conf()
        res_set.read_files_for_base_residue_types(ligand_params)
        pose.conformation().reset_residue_type_set_for_conf(res_set)
    
    # Load pdb_filename into pose
    pyrosetta.io.pose_from_file(pose, pdb_filename)

    # Setup the docking FoldTree
    # the method setup_foldtree takes an input pose and sets its
    #    FoldTree to have jump 1 represent the relation between the two docking
    #    partners, the jump points are the residues closest to the centers of
    #    geometry for each partner with a cutpoint at the end of the chain,
    # the second argument is a string specifying the relative chain orientation
    #    such as "A_B" of "LH_A", ONLY TWO BODY DOCKING is supported and the
    #    partners MUST have different chain IDs and be in the same pose (the
    #    same PDB), additional chains can be grouped with one of the partners,
    #    the "_" character specifies which bodies are separated
    # the third argument...is currently unsupported but must be set (it is
    #    supposed to specify which jumps are movable, to support multibody
    #    docking...but Rosetta doesn't currently)
    # the FoldTrees setup by this method are for TWO BODY docking ONLY!
    dock_jump = 1 # jump number 1 is the inter-body jump
    pyrosetta.rosetta.protocols.docking.setup_foldtree(pose,
                                                       partners,
                                                       pyrosetta.Vector1([dock_jump]))

    # Create ScoreFunctions for centroid and fullatom docking
    scorefxn = pyrosetta.create_score_function("ligand.wts")

    # Setup the high resolution (fullatom) docking protocol using DockMCMProtocol.
    docking = pyrosetta.rosetta.protocols.docking.DockMCMProtocol()
    # Many of its options and settings can be set using the setter methods.
    docking.set_scorefxn(scorefxn)

    # Change directory temporarily for output
    os.chdir(output_dir)
    
    # Setup the PyJobDistributor
    jd = pyrosetta.toolbox.py_jobdistributor.PyJobDistributor(job_output,
                                                              jobs, scorefxn,
                                                              compress=False)
    
    # Set the native pose so that the output scorefile contains the pose rmsd metric
    jd.native_pose = pose 
    
    # Optional: setup a PyMOLObserver
    # pyrosetta.rosetta.protocols.moves.AddPyMOLObserver(test_pose, True)

    # Perform protein-ligand docking
    # counter = 0 # for pretty output to PyMOLObserver
    
    while not jd.job_complete:
        test_pose = pose.clone() # Reset test pose to original structure
        
        # counter += 1 # Change the pose name, for pretty output to PyMOLObserver
        # test_pose.pdb_info().name(job_output + '_' + str(counter))
        
        # Perform docking and output to PyMOL:
        docking.apply(test_pose) 

        # Write the decoy structure to disk:
        jd.output_decoy(test_pose)
    
    os.chdir(working_dir)

Let's test out the sample_ligand_interface function (takes ~2 minutes with jobs=1, which means nstruct is set to 1 in the PyJobDistributor):

In [10]:
if not os.getenv("DEBUG"):
    sample_ligand_interface("inputs/test_lig.pdb", "E_X",
                                  ligand_params=["inputs/TPA.gasteiger.fa.params"],
                                  jobs=1,
                                  job_output="test_lig")
INFO:pyrosetta.rosetta:Found rosetta database at: /mnt/home/klimaj/git/Rosetta/main/source/src/python/PyRosetta/src/pyrosetta/database; using it....
INFO:pyrosetta.rosetta:PyRosetta-4 2019 [Rosetta PyRosetta4.conda.linux.CentOS.python36.Release 2019.39+release.93456a567a8125cafdf7f8cb44400bc20b570d81 2019-09-26T14:24:44] retrieved from: http://www.pyrosetta.org
(C) Copyright Rosetta Commons Member Institutions. Created in JHU by Sergey Lyskov and PyRosetta Team.
INFO:rosetta:core.init: {0} Checking for fconfig files in pwd and ./rosetta/flags
INFO:rosetta:core.init: {0} Rosetta version: PyRosetta4.conda.linux.CentOS.python36.Release r233 2019.39+release.93456a5 93456a567a8125cafdf7f8cb44400bc20b570d81 http://www.pyrosetta.org 2019-09-26T14:24:44
INFO:rosetta:core.init: {0} command: PyRosetta -ex1 -ex2aro -database /mnt/home/klimaj/git/Rosetta/main/source/src/python/PyRosetta/src/pyrosetta/database
INFO:rosetta:basic.random.init_random_generator: {0} 'RNG device' seed mode, using '/dev/urandom', seed=1279767154 seed_offset=0 real_seed=1279767154 thread_index=0
INFO:rosetta:basic.random.init_random_generator: {0} RandomGenerator:init: Normal mode, seed=1279767154 RG_type=mt19937
INFO:rosetta:core.conformation.Conformation: {0} [ WARNING ] Attempted to determine the residue type set of an empty pose.
INFO:rosetta:core.import_pose.import_pose: {0} File 'inputs/test_lig.pdb' automatically determined to be of type PDB
PyRosetta-4 2019 [Rosetta PyRosetta4.conda.linux.CentOS.python36.Release 2019.39+release.93456a567a8125cafdf7f8cb44400bc20b570d81 2019-09-26T14:24:44] retrieved from: http://www.pyrosetta.org
(C) Copyright Rosetta Commons Member Institutions. Created in JHU by Sergey Lyskov and PyRosetta Team.
INFO:rosetta:core.scoring.ScoreFunctionFactory: {0} SCOREFUNCTION: ref2015
INFO:rosetta:core.scoring.ScoreFunctionFactory: {0} SCOREFUNCTION: ref2015
INFO:rosetta:core.scoring.ScoreFunctionFactory: {0} SCOREFUNCTION: ref2015
INFO:rosetta:protocols.docking.DockMCMProtocol: {0} in DockMCMProtocol.apply
Working on decoy: test_lig_0.pdb
INFO:rosetta:protocols.docking.DockMCMProtocol: {0} Using the DockingTaskFactory.
INFO:rosetta:protocols.docking.DockMCMCycle: {0} Setting up defaults for DockMCMCycle:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} ////////////////////////////////////////////////////////////////////////////////
INFO:rosetta:protocols.docking.DockMCMCycle: {0} /// Dockable Jumps: 1                                                        ///
INFO:rosetta:protocols.docking.DockMCMCycle: {0} /// Translation: 0.1                                                         ///
INFO:rosetta:protocols.docking.DockMCMCycle: {0} /// Rotation: 5                                                              ///
INFO:rosetta:protocols.docking.DockMCMCycle: {0} /// Scorefunction:                                                           ///
INFO:rosetta:protocols.docking.DockMCMCycle: {0} ScoreFunction::show():
weights: (fa_atr 0.8) (fa_rep 0.4) (fa_sol 0.6) (fa_elec 0.25) (pro_close 1) (fa_pair 0.8) (hbond_sr_bb 2) (hbond_lr_bb 2) (hbond_bb_sc 2) (hbond_sc 2) (dslf_ss_dst 0.5) (dslf_cs_ang 2) (dslf_ss_dih 5) (dslf_ca_dih 5) (atom_pair_constraint 1) (coordinate_constraint 1) (angle_constraint 1) (dihedral_constraint 1) (omega 0.5) (fa_dun 0.4) (p_aa_pp 0.5) (ref 1) (chainbreak 1)
energy_method_options: EnergyMethodOptions::show: aa_composition_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: mhc_epitope_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: netcharge_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: aspartimide_penalty_value: 25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: etable_type: FA_STANDARD_DEFAULT
analytic_etable_evaluation: 1
EnergyMethodOptions::show: method_weights: ref 0.05 0.09 -0.65 -0.27 1.88 -0.55 1.17 -0.73 -0.42 -0.66 -0.29 -0.76 -0.33 -0.29 -0.77 0 -0.57 -0.57 2.88 0.81
EnergyMethodOptions::show: method_weights: free_res
EnergyMethodOptions::show: unfolded_energies_type: UNFOLDED_SCORE12
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: split_unfolded_label_type: SPLIT_UNFOLDED_MM
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: split_unfolded_value_type: SPLIT_UNFOLDED_BOLTZ
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: atom_vdw_atom_type_set_name: centroid
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: covalent_labeling_input:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: covalent_labeling_fa_input:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_protein_protein_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_RNA_RNA_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_RNA_protein_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_monomer_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_max_dis: 5.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_min_dis: 1.6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_die: 10
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_no_dis_dep_die: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_die: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_D: 80
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_D0: 6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_S: 0.4
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: smooth_fa_elec: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_type: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_param1: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_param2: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_hbond: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grp_cpfxn: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_group_file: /scoring/score_functions/elec_group_def.dat
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_context_dependent: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: use_polarization: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: use_gen_kirkwood: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: protein_dielectric: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: water_dielectric: 78.3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_DNA_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_intra_res_protein: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: count_pair_hybrid: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: count_pair_full: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: put_intra_into_total: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: geom_sol_interres_path_distance_cutoff: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: geom_sol_intrares_path_distance_cutoff: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: eval_intrares_elec_ST_only: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: envsmooth_zero_negatives: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: cst_max_seq_sep: 18446744073709551615
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: pb_bound_tag: bound
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: pb_unbound_tag: unbound
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: ordered_wat_penalty: 1.221
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: ordered_pt_wat_penalty: 2.709
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_ref_seq_length_: 9
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_term_length_: 3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_pssm_feat_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_scorecut_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_scorecut_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_avg_rank_as_energy_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_aa_matrix_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_aa_matrix_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_list_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_list_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_list_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_list_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_containing_cones_cutoff_:6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_cone_distance_cutoff_: 8
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_cone_dotproduct_cutoff_: 0.1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_voxel_grid_padding_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_voxel_size_: 0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_disabled_except_during_packing_: TRUE
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: hbnet_bonus_ramping_function_: "quadratic"
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: hbnet_max_network_size_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_hbond_energy_threshold_: -0.25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_atomic_depth_: 4.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_probe_radius_: 2.3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_resolution_: 0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_oversat_penalty_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_assume_const_backbone_:1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: bond_angle_central_atoms_to_score:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: bond_angle_residue_type_param_set: none
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_DNA_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_intra_res_protein_: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_intra_res_RNA_: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: put_intra_into_total_: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_self_hbonds: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_hb_env_dep: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_hb_env_dep_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: smooth_hb_env_dep: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: bb_donor_acceptor_check: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: decompose_bb_hb_into_pair_energies: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: params_database_tag_: ref2015_params
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_sp2_chi_penalty_: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: sp2_BAH180_rise_: 0.75
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: sp2_outer_width_: 0.357
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: measure_sp3acc_BAH_from_hvy_: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: fade_energy_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_ether_oxygens_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: Mbhbond: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HbondOptions::show: mphbond: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: hbond_energy_shift: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: water_hybrid_sf: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: syn_G_potential_bonus: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: torsion_potential: ps_04282011
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: suiteness_bonus: Richardson
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: rna_base_pair_xy_filename: scoring/rna/rna_base_pair_xy.dat
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_suite_bonus: -1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_2HOprime_bonus: -0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_sugar_bonus: -1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: pack_phosphate_penalty: 0.25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_side_chain_bonus: -0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0}
INFO:rosetta:protocols.docking.DockMCMCycle: {0}
INFO:rosetta:protocols.docking.DockMCMCycle: {0} /// Packing scorefunction:                                                   ///
INFO:rosetta:protocols.docking.DockMCMCycle: {0} ScoreFunction::show():
weights: (fa_atr 1) (fa_rep 0.55) (fa_sol 1) (fa_intra_rep 0.005) (fa_intra_sol_xover4 1) (lk_ball_wtd 1) (fa_elec 1) (pro_close 1.25) (hbond_sr_bb 1) (hbond_lr_bb 1) (hbond_bb_sc 1) (hbond_sc 1) (dslf_fa13 1.25) (omega 0.4) (fa_dun 0.7) (p_aa_pp 0.6) (yhh_planarity 0.625) (ref 1) (rama_prepro 0.45)
energy_method_options: EnergyMethodOptions::show: aa_composition_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: mhc_epitope_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: netcharge_setup_files:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: aspartimide_penalty_value: 25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: etable_type: FA_STANDARD_DEFAULT
analytic_etable_evaluation: 1
EnergyMethodOptions::show: method_weights: ref 1.32468 3.25479 -2.14574 -2.72453 1.21829 0.79816 -0.30065 2.30374 -0.71458 1.66147 1.65735 -1.34026 -1.64321 -1.45095 -0.09474 -0.28969 1.15175 2.64269 2.26099 0.58223
EnergyMethodOptions::show: method_weights: free_res
EnergyMethodOptions::show: unfolded_energies_type: UNFOLDED_SCORE12
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: split_unfolded_label_type: SPLIT_UNFOLDED_MM
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: split_unfolded_value_type: SPLIT_UNFOLDED_BOLTZ
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: atom_vdw_atom_type_set_name: centroid
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: covalent_labeling_input:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: covalent_labeling_fa_input:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_protein_protein_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_RNA_RNA_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_RNA_protein_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_monomer_fa_elec: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_max_dis: 5.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_min_dis: 1.6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_die: 10
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_no_dis_dep_die: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_die: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_D: 80
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_D0: 6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_sigmoidal_S: 0.4
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: smooth_fa_elec: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_type: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_param1: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_param2: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_fade_hbond: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grp_cpfxn: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: elec_group_file: /scoring/score_functions/elec_group_def.dat
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: grpelec_context_dependent: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: use_polarization: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: use_gen_kirkwood: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: protein_dielectric: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: water_dielectric: 78.3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_DNA_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: exclude_intra_res_protein: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: count_pair_hybrid: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: count_pair_full: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: put_intra_into_total: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: geom_sol_interres_path_distance_cutoff: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: geom_sol_intrares_path_distance_cutoff: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: eval_intrares_elec_ST_only: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: envsmooth_zero_negatives: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: cst_max_seq_sep: 18446744073709551615
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: pb_bound_tag: bound
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: pb_unbound_tag: unbound
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: ordered_wat_penalty: 1.221
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: ordered_pt_wat_penalty: 2.709
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_ref_seq_length_: 9
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_term_length_: 3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_pssm_feat_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_scorecut_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_scorecut_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_avg_rank_as_energy_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_aa_matrix_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_aa_matrix_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_list_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_list_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_list_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_list_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_defined_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: nmer_svm_rank_:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_containing_cones_cutoff_:6
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_cone_distance_cutoff_: 8
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_cone_dotproduct_cutoff_: 0.1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_voxel_grid_padding_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_voxel_size_: 0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: voids_penalty_energy_disabled_except_during_packing_: TRUE
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: hbnet_bonus_ramping_function_: "quadratic"
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: hbnet_max_network_size_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_hbond_energy_threshold_: -0.25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_atomic_depth_: 4.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_probe_radius_: 2.3
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_burial_resolution_: 0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_oversat_penalty_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: approximate_buried_unsat_penalty_assume_const_backbone_:1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: bond_angle_central_atoms_to_score:
INFO:rosetta:protocols.docking.DockMCMCycle: {0} EnergyMethodOptions::show: bond_angle_residue_type_param_set: none
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_DNA_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_intra_res_protein_: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_intra_res_RNA_: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: put_intra_into_total_: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_self_hbonds: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_hb_env_dep: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_hb_env_dep_DNA: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: smooth_hb_env_dep: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: bb_donor_acceptor_check: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: decompose_bb_hb_into_pair_energies: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: params_database_tag_: ref2015_params
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: use_sp2_chi_penalty_: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: sp2_BAH180_rise_: 0.75
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: sp2_outer_width_: 0.357
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: measure_sp3acc_BAH_from_hvy_: true
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: fade_energy_: 1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: exclude_ether_oxygens_: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: Mbhbond: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HbondOptions::show: mphbond: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: hbond_energy_shift: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} HBondOptions::show: water_hybrid_sf: false
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: syn_G_potential_bonus: 0
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: torsion_potential: ps_04282011
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: suiteness_bonus: Richardson
INFO:rosetta:protocols.docking.DockMCMCycle: {0} RNA_EnergyMethodOptions::show: rna_base_pair_xy_filename: scoring/rna/rna_base_pair_xy.dat
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_suite_bonus: -1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_2HOprime_bonus: -0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_sugar_bonus: -1
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: pack_phosphate_penalty: 0.25
INFO:rosetta:protocols.docking.DockMCMCycle: {0} FreeDOF_Options::show: free_side_chain_bonus: -0.5
INFO:rosetta:protocols.docking.DockMCMCycle: {0}
INFO:rosetta:protocols.docking.DockMCMCycle: {0}
INFO:rosetta:protocols.docking.DockMCMCycle: {0} ////////////////////////////////////////////////////////////////////////////////
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 964 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 985 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 985 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 985 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 985 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.pack_rotamers: {0} built 985 rotamers at 39 positions.
INFO:rosetta:core.pack.interaction_graph.interaction_graph_factory: {0} Instantiating DensePDInteractionGraph
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
INFO:rosetta:core.pack.task: {0} Packer task: initialize from command line()
INFO:rosetta:core.pack.rotamer_set.RotamerSet_: {0} Using simple Rotamer generation logic for TPA
CPU times: user 2min 10s, sys: 457 ms, total: 2min 10s
Wall time: 2min 12s

Interpreting Results:

The PyJobDistributor will output the lowest scoring pose for each trajectory (as a .pdb file), recording the score in outputs/<job_output>.fasc. Generally, the decoy generated with the lowest score contains the best prediction for the protein-ligand conformation. PDB files produced from docking will contain both docking partners in their predicted conformation. When inspecting these PDB files (or the PyMOLObserver output) be aware that PyMOL can introduce or predict bonds that do not exist, particularly for close atoms. This rarely occurs when using the PyMOLMover.keep_history feature (since PyRosetta will sample some conformation space that has clashes).

The PyMOLObserver will output a series of structures directly produced by the DockingProtocol. Unfortunately, this may include intermediate structures that do not yield any insight into the protocol performance. A LARGE number of structures are output to PyMOL and your machine may have difficulty loading all of these structures. If this occurs, try changing the PyMOLObserver keep_history to False or running the protocol without the PyMOLObserver.

Interface structure prediction is useful for considering what physical properties are important in the binding event and what conformational changes occur. Once experienced using PyRosetta, you can easily write scripts to investigate the Rosetta score terms and structural characteristics. There is no general interpretation of ligand-binding results. Although Rosetta score does not translate directly to physical meaning (it is not physical energy), splitting the docked partners and comparing the scores (after packing or refinement) can indicate the strength of the bonding interaction.


Restart Jupyter Notebook kernel to properly re-initialize PyRosetta


In [1]:
import sys

# Notebook setup
if 'google.colab' in sys.modules:
    !pip install pyrosettacolabsetup
    import pyrosettacolabsetup
    pyrosettacolabsetup.mount_pyrosetta_install()
    print ("Notebook is set for PyRosetta use in Colab.  Have fun!")
    
    
import logging
logging.basicConfig(level=logging.INFO)
import os
import pyrosetta
import pyrosetta.distributed
import pyrosetta.distributed.viewer as viewer
In [2]:
params_file = "inputs/TPA.gasteiger.fa.params"
flags = f"""
-extra_res_fa {params_file}
-ignore_unrecognized_res 1
-mute all
"""
pyrosetta.distributed.init(flags)
pose = pyrosetta.io.pose_from_file("expected_outputs/test_lig_0.pdb")
INFO:pyrosetta.distributed:maybe_init performing pyrosetta initialization: {'extra_options': '-extra_res_fa inputs/TPA.gasteiger.fa.params -ignore_unrecognized_res 1 -mute all', 'silent': True}
INFO:pyrosetta.rosetta:Found rosetta database at: /mnt/home/klimaj/git/Rosetta/main/source/src/python/PyRosetta/src/pyrosetta/database; using it....
INFO:pyrosetta.rosetta:PyRosetta-4 2019 [Rosetta PyRosetta4.conda.linux.CentOS.python36.Release 2019.39+release.93456a567a8125cafdf7f8cb44400bc20b570d81 2019-09-26T14:24:44] retrieved from: http://www.pyrosetta.org
(C) Copyright Rosetta Commons Member Institutions. Created in JHU by Sergey Lyskov and PyRosetta Team.

After ligand refinement has completed, let's take a look at the output .pdb file using the py3Dmol module:

In [9]:
chE = pyrosetta.rosetta.core.select.residue_selector.ChainSelector("E")

view = viewer.init(pose)
view.add(viewer.setStyle())
view.add(viewer.setStyle(command=({"hetflag": True}, {"stick": {"colorscheme": "brownCarbon", "radius": 0.2}})))
view.add(viewer.setSurface(residue_selector=chE, opacity=0.7, color='white'))
view.add(viewer.setHydrogenBonds())
view()

You appear to be running in JupyterLab (or JavaScript failed to load for some other reason). You need to install the 3dmol extension:
jupyter labextension install jupyterlab_3dmol