kernel/nup84.py

Modify solve for a Nup84-like structure using a mix of rigid bodies and coarse grained models using crosslinking data. In addition, show how to visualize restraints and visualize the rejected conformations. Both are useful things to do when trying to figure out why optimization is not converging.

## \example kernel/nup84.py
# Modify solve for a Nup84-like structure using a mix of rigid bodies
# and coarse grained models using crosslinking data. In
# addition, show how to visualize restraints and visualize the
# rejected conformations. Both are useful things to do when trying to
# figure out why optimization is not converging.

from __future__ import print_function
import IMP
import IMP.atom
import IMP.container
import IMP.display
import IMP.statistics
import IMP.example
import os
import sys

# not finished
IMP.add_bool_flag("run", "Whether to run the program")

# parse command line arguments so, eg profiling can be used
IMP.setup_from_argv(sys.argv, "Nup84 example")

if IMP.get_bool_flag("run") != "yes":
    exit(0)

# First we define some basic parameters for the modeling effort

# the spring constant to use, it doesn't really matter
k = 10
# the target resolution for the representation
resolution = 100
# the box to perform everything in, make it flat as it is a 2D structure
bb = IMP.algebra.BoundingBox3D(IMP.algebra.Vector3D(-300, -300, -50),
                               IMP.algebra.Vector3D(300, 300, 50))

# how many times to try to find a good solution
number_of_sampling_attempts = 1
number_of_mc_steps = 10000

# Create a coarse grained protein with a given name, adding it to universe


def add_protein_from_length(model, name, residues, parent, restraints,
                            excluded_volume_particles, optimized_particles):
    # Create a coarse grained protein with the passed residue information
    h = IMP.atom.create_protein(model, name, resolution, residues)

    parent.add_child(h)
    # Here, each of the constituent particles will be optimized independently
    leaves = IMP.atom.get_leaves(h)
    optimized_particles.extend(leaves)
    excluded_volume_particles.extend(leaves)

    # Ensure that the various particles of the protein stay connected
    r = IMP.atom.create_connectivity_restraint([IMP.atom.Selection(c)
                                                for c in h.get_children()], k,
                                               "connect " + name)

    if r:
        # make sure there is an actual restraint
        restraints.append(r)
        r.set_maximum_score(k)

# Create protein as a rigid body from a pdb file


def add_protein_from_pdb(model, name, file, parent, restraints,
                         excluded_volume_particles, optimized_particles):
    # we should keep the original particles around so they get written

    # create an atomic representation from the pdb file
    t = IMP.atom.read_pdb(
        IMP.get_example_path(os.path.join("data", file)), model,
        IMP.atom.ATOMPDBSelector())
    # extract the chain from the file
    c = IMP.atom.Chain(IMP.atom.get_by_type(t, IMP.atom.CHAIN_TYPE)[0])
    # there is no reason to use all atoms, just approximate the pdb shape
    # instead
    s = IMP.atom.create_simplified_along_backbone(c, resolution / 2.0, True)
    s.set_name(name)
    # tear down what is left
    IMP.atom.destroy(t)
    # make the simplified structure rigid
    rb = IMP.atom.create_rigid_body(s)
    rb.set_coordinates_are_optimized(True)
    optimized_particles.append(rb)
    excluded_volume_particles.extend(s.get_children())
    parent.add_child(s)


# Create protein as a rigid body from several pdb file
def add_protein_from_pdbs(model, name, files, parent, restraints,
                          excluded_volume_particles, optimized_particles):
    h = IMP.atom.Hierarchy.setup_particle(IMP.Particle(model, name))
    for i, f in enumerate(files):
        add_protein_from_pdb(model, name + str(i), f, h, restraints,
                             excluded_volume_particles, optimized_particles)
    r = IMP.atom.create_connectivity_restraint([IMP.atom.Selection(c, hierarchy_types=[IMP.atom.FRAGMENT_TYPE])
                                                for c in h.get_children()],
                                               k, "connect " + name)
    if r:
        restraints.append(r)
        r.set_maximum_score(k)

# Create all the needed representation using the above functions


def create_representation(model):
    restraints = []
    optimized_particles = []
    excluded_volume_particles = []
    universe = IMP.atom.Hierarchy.setup_particle(
        IMP.Particle(model, "the universe"))

    add_protein_from_length(model, "Nup85", 570, universe, restraints,
                            excluded_volume_particles, optimized_particles)

    # pin the c-terminus
    ct = IMP.atom.Selection(universe, molecule="Nup85",
                            hierarchy_types=[IMP.atom.FRAGMENT_TYPE],
                            terminus=IMP.atom.Selection.C)
    d = IMP.core.XYZ(ct.get_selected_particles()[0])
    d.set_coordinates(IMP.algebra.Vector3D(0, 0, 0))
    d.set_coordinates_are_optimized(False)

    add_protein_from_length(model, "Nup84", 460, universe, restraints,
                            excluded_volume_particles, optimized_particles)
    add_protein_from_length(model, "Nup145C", 442, universe, restraints,
                            excluded_volume_particles, optimized_particles)
    add_protein_from_length(
        model, "Nup120", [0, 500, 761], universe, restraints,
        excluded_volume_particles, optimized_particles)
    add_protein_from_length(
        model, "Nup133", [0, 450, 778, 1160], universe, restraints,
        excluded_volume_particles, optimized_particles)
    add_protein_from_pdb(model, "Seh1", "seh1.pdb", universe, restraints,
                         excluded_volume_particles, optimized_particles)
    add_protein_from_pdb(model, "Sec13", "sec13.pdb", universe, restraints,
                         excluded_volume_particles, optimized_particles)
    return universe, restraints, excluded_volume_particles, optimized_particles


def add_distance_restraint(selection0, selection1, name, restraints):
    r = IMP.atom.create_distance_restraint(selection0, selection1, 0, k, name)
    r.set_maximum_score(k)
    restraints.append(r)


def encode_data_as_restraints(universe, restraints):
    s0 = IMP.atom.Selection(
        hierarchy=universe, hierarchy_types=[IMP.atom.FRAGMENT_TYPE],
        molecule="Nup145C", residue_indexes=[(0, 423)])
    s1 = IMP.atom.Selection(
        hierarchy=universe, hierarchy_types=[IMP.atom.FRAGMENT_TYPE],
        molecule="Nup84")
    s2 = IMP.atom.Selection(
        hierarchy=universe, hierarchy_types=[IMP.atom.FRAGMENT_TYPE],
        molecule="Sec13")
    r = IMP.atom.create_connectivity_restraint(
        [s0, s1, s2], k, "Nup145C Nup84 Sec13")
    r.set_maximum_score(k)
    restraints.append(r)

    add_distance_restraint(
        IMP.atom.Selection(hierarchy=universe, molecule="Nup145C",
                           residue_indexes=[(0, 423)],
                           hierarchy_types=[
                               IMP.atom.FRAGMENT_TYPE]),
        IMP.atom.Selection(
            hierarchy=universe, molecule="Nup85",
            hierarchy_types=[
                IMP.atom.FRAGMENT_TYPE]),
        "Num145C, Nup85", restraints)
    add_distance_restraint(
        IMP.atom.Selection(hierarchy=universe, molecule="Nup145C",
                           residue_indexes=[(0, 423)],
                           hierarchy_types=[
                               IMP.atom.FRAGMENT_TYPE]),
        IMP.atom.Selection(
            hierarchy=universe, molecule="Nup120",
            residue_indexes=[(500, 762)],
            hierarchy_types=[
                IMP.atom.FRAGMENT_TYPE]),
        "Nup145C Nup120", restraints)
    add_distance_restraint(
        IMP.atom.Selection(hierarchy=universe, molecule="Nup84",
                           hierarchy_types=[
                               IMP.atom.FRAGMENT_TYPE]),
        IMP.atom.Selection(
            hierarchy=universe, molecule="Nup133",
            residue_indexes=[(778, 1160)],
            hierarchy_types=[
                IMP.atom.FRAGMENT_TYPE]),
        "Nup84 Nup133", restraints)
    add_distance_restraint(
        IMP.atom.Selection(hierarchy=universe, molecule="Nup85",
                           hierarchy_types=[
                               IMP.atom.FRAGMENT_TYPE]),
        IMP.atom.Selection(
            hierarchy=universe, molecule="Seh1",
            hierarchy_types=[
                IMP.atom.FRAGMENT_TYPE]),
        "Nup85 Seh1", restraints)
    add_distance_restraint(
        IMP.atom.Selection(hierarchy=universe, molecule="Nup145C",
                           residue_indexes=[(0, 423)],
                           hierarchy_types=[
                               IMP.atom.FRAGMENT_TYPE]),
        IMP.atom.Selection(
            hierarchy=universe, molecule="Sec13",
            hierarchy_types=[
                IMP.atom.FRAGMENT_TYPE]),
        "Nup145C Sec13", restraints)


# find acceptable conformations of the model
def get_configurations(
    model,
    restraints,
    excluded_volume_particles,
        optimized_particles):
    #cpc= IMP.container.ClosePairContainer(representation.get_particles(), 0, 10)
    # evr= IMP.container.PairRestraint(IMP.core.SoftSpherePairScore(k), cpc,
    #                                 "Excluded Volume")
    scale = .5
    mc = IMP.core.MonteCarlo(model)
    movers = []
    for p in optimized_particles:
        if IMP.core.RigidBody.get_is_setup(p):
            mover = IMP.core.RigidBodyMover(
                p, IMP.core.XYZR(p).get_radius() * scale,
                .2 * scale)
            movers.append(mover)
        else:
            mover = IMP.core.BallMover(model,
                [p], IMP.core.XYZR(p).get_radius() * scale)
            movers.append(mover)
    serial_mover = IMP.core.SerialMover(movers)
    mc.add_mover(serial_mover)
    scoring_function = IMP.core.IncrementalScoringFunction(
        optimized_particles, restraints)
    scoring_function.add_close_pair_score(IMP.core.SoftSpherePairScore(k), 0.0,
                                          excluded_volume_particles)

    configuration_set = IMP.ConfigurationSet(model)
    # must write our own sampler as IMP.core.MCCGSampler doesn't handle rigid
    # bodies
    for i in range(number_of_sampling_attempts):
        for p in optimized_particles:
            IMP.core.XYZ(p).set_coordinates(
                IMP.algebra.get_random_vector_in(bb))
        mc.optimize(number_of_mc_steps)
        if scoring_function.get_had_good_score():
            configuration_set.save()
    return configuration_set


model = IMP.Model()
universe, restraints, excluded_volume_particles, optimized_particles = create_representation(
    model)
encode_data_as_restraints(universe, restraints)

configuration_set = get_configurations(model, restraints,
                                       excluded_volume_particles,
                                       optimized_particles)

print("Found", configuration_set.get_number_of_configurations(), "good configurations")

# now lets save them all to a file
rmf_file_name = IMP.create_temporary_file_name("nup84", ".rmf")
rmf = RMF.create_rmf_file(rmf_file_name)

# we want to see the scores of the various restraints also
IMP.rmf.add_restraints(rmf, restraints)
# and the actual structures
IMP.rmf.add_hierarchy(rmf, universe)

for i in range(0, configuration_set.get_number_of_configurations()):
    configuration_set.load_configuration(i)
    # align all the configurations with the first so they display nicely
    # if we want to be fancy we can account for flips too
    if i == 0:
        base_coords = [IMP.core.XYZ(p).get_coordinates()
                       for p in optimized_particles]
    else:
        tr = IMP.algebra.get_transform_taking_first_to_second(
            optimized_particles, base_coords)
        IMP.core.transform(optimized_particles, tr)
    # update the restraint scores
    sf.evaluate(False)
    IMP.rmf.save_frame(rmf, str(i))

print("You can now open", rmf_file_name, "in chimera")