PyRosetta (15) Rigid Body Movers & Docking

protein design
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PyRosetta (15): Rigid Body Movers & Docking

Introduction

The fundamental docking move is a rigid-body transformation consisting of a translation and rotation. Any rigid body move also needs to know which part moves and which part is fixed. In Rosetta, this division is known as a Jump and the set of protein segments and jumps are stored in an object attached to a pose called a FoldTree.

Rigid body movers are components of protein docking protocols.

Initiation

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import pyrosetta
from pyrosetta import rosetta
import pyrosetta.rosetta.protocols.rigid as rigid
import pyrosetta.rosetta.protocols.docking as docking
pyrosetta.init()

Manual rotation and translation

RigidBodySpinMover class

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# load pose
pose = pyrosetta.pose_from_pdb("input.pdb")
 
# instantiating RigidBodyTransMover
trans_mover = rigid.RigidBodyTransMover(pose, 1)
 
# set Z-axis as the translation (sliding); Set sliding distance to 5 Å
trans_axis = rosetta.numeric.xyzVector_double_t(0, 0, 1)
trans_mover.trans_axis(trans_axis)
trans_mover.step_size(5.0)
 
# apply RigidBodyTransMover
trans_mover.apply(pose)
 
# save pose as pdb
pose.dump_pdb("translated_output.pdb")

RigidBodyTransMover class

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# load pose
pose = pyrosetta.pose_from_pdb("input.pdb")
 
# Instantiating RigidBodySpinMover
spin_mover = rigid.RigidBodySpinMover()
rotation_axis = xyzVector_double_t(0.0, 0.0, 1.0)
rotation_angle = 45.0  # degree

# Set spin axis
spin_mover.spin_axis(rotation_axis)

# Set rotation angle (in degree)
spin_mover.spin_mag(rotation_angle)
 
# Apply RigidBodySpinMover
spin_mover.apply(pose)
 
# save pose as pdb
pose.dump_pdb("spinned_output.pdb")

RigidBodyRandomizeMover

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# sliding 1st jump
jump_num = 1

# `partner_upstream`: the first chain in pose
# `partner_downstream`: the second chain in pose
randomize1 = rigid.RigidBodyRandomizeMover(my_pose, jump_num, rigid.partner_upstream)
randomize2 = rigid.RigidBodyRandomizeMover(my_pose, jump_num, rigid.partner_downstream)

Slide into contact: DockingSlideIntoContactMover/ FADockingSlideIntoContactMover

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# load pose
pose = pyrosetta.pose_from_pdb("input.pdb")
 
# Instantiating DockingSlideIntoContactMover
slide_mover = docking.DockingSlideIntoContactMover(1)  # sliding jump 1
#slide_mover = FaDockingSlideIntoContact(jump_num)  # for full-atom mode
slide_mover.apply(pose)
 
# Save pose
pose.dump_pdb("slide_into_contact_output.pdb")

Low Resolution Global Docking Mover: DockingLowRes

The argument "A_B" tells Rosetta to make chain A the “rigid” chain and allow chain B to move.

If there were more chains in the pdb structure, supplying "AB_C" would hold chains A and B rigid together as a single unit and allow chain C to move.

The third argument Vector1([1]) is required, it creates a Rosetta vector object — indexed from 1 — with one element that identifies the first Jump in the FoldTree for docking use.

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# Assume that we have a `Pose` object named `cen_pose`
# 1st jump
jump_num = 1
dock_lowres = DockingLowRes(scorefxn_low, jump_num)

# Setup Fold Tree
setup_foldtree(cen_pose,"A_B",Vector1([1]))

# Apply to cen_pose
dock_lowres.apply(cen_pose)

High Resolution Global Docking Mover: DockMCMProtocol

The high-resolution stage of RosettaDock is also available as a Mover. This mover encompasses random rigid-body moves, side-chain packing, and gradient-based minimization in the rigid-body coordinates. High-resolution docking needs an all-atom score function. The optimized docking weights are available as a patch to the standard all-atom energy function.

Unlike for DockingLowRes, we must supply the docking partners with "A_B" instead of jump_num.

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# Assume that we have a `Pose` object named `cen_pose`
scorefxn_high = create_score_function("ref2015.wts", "docking")

# Instantiating high resolution global docking mover
dock_hi_res = DockMCMProtocol()
dock_hi_res.set_scorefxn(scorefxn_high)

# Setup Fold Tree
setup_foldtree(cen_pose,"A_B",Vector1([1]))

dock_hi_res.set_partners("A_B")  # make sure the FoldTree is set up properly

# Apply
dock_hi_res.apply(my_pose)

# Copy the side chains from the original monomer structures
recover_sidechains = ReturnSidechainMover(starting_pose)
recover_sidechains.apply(my_pose)

# Or, we can use a `PackRotamersMover`
# my_tf = TaskFactory()
# my_tf.push_back(operation.InitializeFromCommandline()) 
# my_tf.push_back(operation.RestrictToRepacking()) 
# my_packer = pyrosetta.rosetta.protocols.minimization_packing.PackRotamersMover() 
# my_packer.task_factory(my_tf) 
# my_packer.apply(my_pose)

Docking Using XML

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xml = pyrosetta.rosetta.protocols.rosetta_scripts.XmlObjects.create_from_string("""
<ROSETTASCRIPTS>
  <SCOREFXNS>
    <ScoreFunction name="fa_standard" weights="ref2015.wts"/> `ref2015.wts` score function
  </SCOREFXNS>
  <RESIDUE_SELECTORS>
    <Chain name="chX" chains="X"/> select chain "X" in pose
  </RESIDUE_SELECTORS>
  <SIMPLE_METRICS>
    <RMSDMetric name="rmsd_chX" residue_selector="chX" reference_name="store_native" residue_selector_ref="chX" robust="true" rmsd_type="rmsd_all" /> 
    Measurement using RMSD of chain X
  </SIMPLE_METRICS>
  <SCORINGGRIDS ligand_chain="X" width="25">
    <ClassicGrid grid_name="vdw" weight="1.0"/> 
    Grids are recalculated if any non-ligand atoms change position. 
    The weight specified for each grid is multiplied by the ligand score for that grid.
  </SCORINGGRIDS>
  <LIGAND_AREAS>
    <LigandArea name="docking_sidechain_X" chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true" minimize_ligand="10"/>
    <LigandArea name="final_sidechain_X" chain="X" cutoff="6.0" add_nbr_radius="true" all_atom_mode="true"/>
    <LigandArea name="final_backbone_X" chain="X" cutoff="7.0" add_nbr_radius="false" all_atom_mode="true" Calpha_restraints="0.3"/>
  </LIGAND_AREAS>
  <INTERFACE_BUILDERS>
    <InterfaceBuilder name="side_chain_for_docking" ligand_areas="docking_sidechain_X"/>
    <InterfaceBuilder name="side_chain_for_final" ligand_areas="final_sidechain_X"/>
    <InterfaceBuilder name="backbone" ligand_areas="final_backbone_X" extension_window="3"/>
  </INTERFACE_BUILDERS>
  <MOVEMAP_BUILDERS>
    <MoveMapBuilder name="docking" sc_interface="side_chain_for_docking" minimize_water="true"/>
    <MoveMapBuilder name="final" sc_interface="side_chain_for_final" bb_interface="backbone" minimize_water="true"/>
  </MOVEMAP_BUILDERS>
  <MOVERS>
    <SavePoseMover name="spm" restore_pose="0" reference_name="store_native"/>
    <Transform name="transform" chain="X" box_size="20.0" move_distance="10" angle="360" initial_perturb="2" cycles="500" repeats="5" temperature="1000"/>
    <HighResDocker name="high_res_docker" cycles="9" repack_every_Nth="3" scorefxn="fa_standard" movemap_builder="docking"/>
    <FinalMinimizer name="final" scorefxn="fa_standard" movemap_builder="final"/>
  </MOVERS>
  <FILTERS>
      <LigInterfaceEnergy name="interfE" scorefxn="fa_standard" energy_cutoff="0.0" confidence="0"/>
      <SimpleMetricFilter name="rmsd_chX" metric="rmsd_chX" cutoff="999999." comparison_type="lt" confidence="0"/>
  </FILTERS>
  <PROTOCOLS>
    <Add mover="spm"/>
    <Add mover="transform"/>
    <Add mover="high_res_docker"/>
    <Add mover="final"/>
    <Add filter="interfE"/>
    <Add filter="rmsd_chX"/>
  </PROTOCOLS>
</ROSETTASCRIPTS>
""").get_mover("ParsedProtocol")
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