def write_equilibrium_trajectory(trajectory: md.Trajectory,
trajectory_filename: str) -> float:
"""
Write the results of an equilibrium simulation to disk. This task will append the results to the given filename.
Arguments
----------
trajectory : md.Trajectory
the trajectory resulting from an equilibrium simulation
trajectory_filename : str
the name of the trajectory file to which we should append
Returns
-------
True
"""
if not os.path.exists(trajectory_filename):
trajectory.save_hdf5(trajectory_filename)
_logger.debug(
f"{trajectory_filename} does not exist; instantiating and writing to."
)
else:
_logger.debug(f"{trajectory_filename} exists; appending.")
written_traj = md.load_hdf5(trajectory_filename)
concatenated_traj = written_traj.join(trajectory)
concatenated_traj.save_hdf5(trajectory_filename)
return True
def write_equilibrium_trajectory(equilibrium_result: EquilibriumResult, trajectory: md.Trajectory, trajectory_filename: str) -> float:
"""
Write the results of an equilibrium simulation to disk. This task will append the results to the given filename.
Parameters
----------
equilibrium_result : EquilibriumResult namedtuple
the result of an equilibrium calculation
trajectory : md.Trajectory
the trajectory resulting from an equilibrium simulation
trajectory_filename : str
the name of the trajectory file to which we should append
Returns
-------
reduced_potential_final_frame : float
the reduced potential of the final frame
"""
if not os.path.exists(trajectory_filename):
trajectory.save_hdf5(trajectory_filename)
else:
written_traj = md.load_hdf5(trajectory_filename)
concatenated_traj = written_traj.join(trajectory)
concatenated_traj.save_hdf5(trajectory_filename)
return equilibrium_result.reduced_potential
def write_equilibrium_trajectory(equilibrium_result: EquilibriumResult,
trajectory: md.Trajectory,
trajectory_filename: str) -> float:
"""
Write the results of an equilibrium simulation to disk. This task will append the results to the given filename.
Parameters
----------
equilibrium_result : EquilibriumResult namedtuple
the result of an equilibrium calculation
trajectory : md.Trajectory
the trajectory resulting from an equilibrium simulation
trajectory_filename : str
the name of the trajectory file to which we should append
Returns
-------
reduced_potential_final_frame : float
the reduced potential of the final frame
"""
if not os.path.exists(trajectory_filename):
trajectory.save_hdf5(trajectory_filename)
else:
written_traj = md.load_hdf5(trajectory_filename)
concatenated_traj = written_traj.join(trajectory)
concatenated_traj.save_hdf5(trajectory_filename)
return equilibrium_result.reduced_potential
def load_frame(base_dir, protein, filename, frame_index):
"""
:param base_dir: Project's base dir
:param protein: Protein of interest
:param filename: file to load
:param frame_index: needed frame
:return: The required frame
"""
os.chdir(os.path.join(base_dir, protein))
filename = os.path.splitext(filename)[0]
return mdt.load_hdf5(filename="./protein_traj/%s.hdf5" % filename,
frame=frame_index)
def extract_aligned_prot_lig_wat_traj(md_components,
flask,
trj_fn,
opt,
nmax=30,
water_cutoff=15.0):
"""
Extracts the aligned protein trajectory and aligned ligand trajectory and aligned
Water trajectory from a MD trajectory of a larger system that includes other
components (eg water).
The passed in setup mol must have the topology that matches the trajectory, and its xyz
coordinates are the reference for the alignment. The alignment is done on the
alpha carbons (atom name CA) of the active site residues within cutoff
from the ligand. Once the alignment is done, the protein and ligand trajectories
are each placed into a separate OEMol, one conformer per trajectory frame.
Water trajectory is selecting the nmax waters from the ligand and protein CA
within the cutoff distance for each trajectory snapshot
Inputs:
md_components: MDComponents object
The md components carrying the setup starting flask.
flask: OEMol
The system flask
trj_fn: String
The filename of the hdf5-format MD trajectory or Gromacs .trr file format
water_cutoff: Float
The cutoff distance between the PL binding site and the waters in angstroms
nmax: Integer
max number of waters to select
Outputs:
multi_conf_protein: A multi conformer OEMol for the protein, one conformer per frame.
multi_conf_ligand: A multi conformer OEMol for the ligand, one conformer per frame.
multi_conf_water: A multi conformer OEMol for the waters, one conformer per frame.
"""
# Extract protein, ligand, water and excipients from the flask
# protein, ligand, water, excipients = oeommutils.split(flask, ligand_res_name="LIG")
set_up_flask, map_dic = md_components.create_flask
protein = md_components.get_protein
ligand = md_components.get_ligand
check_nmax = nmax_waters(protein, ligand, water_cutoff)
if check_nmax < nmax:
opt['Logger'].warn(
"The selected number of max waters cannot fit around the protein binding site: {} vs {}"
.format(nmax, check_nmax))
void, traj_ext = os.path.splitext(trj_fn)
traj_dir = os.path.dirname(trj_fn)
if traj_ext == '.h5':
trj = md.load_hdf5(trj_fn)
elif traj_ext == '.trr':
pdb_fn = glob.glob(os.path.join(traj_dir, '*.pdb'))[0]
trj = md.load_trr(trj_fn, top=pdb_fn)
trj = trj[1:]
else:
raise ValueError(
"Trajectory file format {} not recognized in the trajectory {}".
format(traj_ext, trj_fn))
# System topology
top_trj = trj.topology
# Ligand indexes
# lig_idx = top_trj.select("resname LIG")
lig_idx = map_dic['ligand']
# Protein indexes
# prot_idx = top_trj.select("protein")
# It is safer to use OE toolkits than mdtraj which is missing the protein caps
prot_idx = map_dic['protein']
# for at in protein.GetAtoms():
# prot_idx.append(at.GetIdx())
# Water oxygen indexes
water_O_idx = top_trj.select("water and element O")
# Protein carbon alpha indexes
prot_ca_idx = top_trj.select("backbone and element C")
# Cutoff for the selection of the binding site atoms in A
cutoff_bs = 5.0
# Carbon alpha binding site indexes
ca_bs_idx = md.compute_neighbors(trj[0],
cutoff_bs / 10.0,
lig_idx,
haystack_indices=prot_ca_idx,
periodic=True)[0]
# Carbon alpha binding site and ligand indexes
ca_bs_lig_idx = np.concatenate((ca_bs_idx, lig_idx))
# Image the protein-ligand trajectory so the complex does not jump across box boundaries
protlig = trj[0].atom_slice(np.concatenate((prot_idx, lig_idx)))
protligAtoms = [atom for atom in protlig.topology.atoms]
with open(os.devnull, 'w') as devnull:
with contextlib.redirect_stderr(devnull):
trjImaged = trj.image_molecules(inplace=False,
anchor_molecules=[protligAtoms],
make_whole=True)
# trjImaged = trj.image_molecules(inplace=False, anchor_molecules=[protligAtoms], make_whole=True)
count = 0
water_max_frames = []
# TODO DEBUG
# trjImaged = trjImaged[:10]
for frame in trjImaged:
# print(count, flush=True)
# Water oxygen binding site indexes
water_O_bs_idx = md.compute_neighbors(frame,
water_cutoff / 10.0,
ca_bs_lig_idx,
haystack_indices=water_O_idx,
periodic=True)
# Pair combination water indexes times ligand indexes
wat_lig_pairs = np.array(np.meshgrid(water_O_bs_idx,
lig_idx)).T.reshape(-1, 2)
# Distances between the waters and the ligand in nm
wat_lig_distances = md.compute_distances(frame,
wat_lig_pairs,
periodic=True,
opt=True)
# Reshape the wat_lig_distances
ns = np.reshape(wat_lig_distances,
(len(water_O_bs_idx[0]), len(lig_idx)))
# Min distances in nm between the oxygen waters and the ligand
min_wat_O_lig_distances = np.min(ns, axis=1)
# Pair combination water indexes times protein binding site carbon alpha indexes
wat_ca_bs_pairs = np.array(np.meshgrid(water_O_bs_idx,
ca_bs_idx)).T.reshape(-1, 2)
# Distances between the waters and the protein binding site carbon alpha in nm
wat_ca_bs_distances = md.compute_distances(frame,
wat_ca_bs_pairs,
periodic=True,
opt=True)
# Reshape the wat_ca_bs_distances
ns = np.reshape(wat_ca_bs_distances,
(len(water_O_bs_idx[0]), len(ca_bs_idx)))
# Min distances in nm between the oxygen waters and the protein binding site carbon alpha
min_wat_O_ca_bs_distances = np.min(ns, axis=1)
metrics = min_wat_O_lig_distances + min_wat_O_ca_bs_distances
metric_distances = dict()
for wat_idx, m in zip(water_O_bs_idx[0], metrics):
metric_distances[int(wat_idx)] = m
water_list_sorted_max = sorted(metric_distances.items(),
key=lambda x: x[1])[:nmax]
if len(water_list_sorted_max) != nmax:
raise ValueError(
"The ordered water list has the wrong size {} vs expected {} for the frame {}"
.format(len(water_list_sorted_max), nmax, count))
water_max_frames.append(water_list_sorted_max)
# print(min_wat_O_ca_bs_distances)
# print(pairs[:len(lig_idx), :])
# for p,d in zip(wat_ca_bs_pairs, wat_ca_bs_distances[0]):
# print(p,d)
count += 1
# Put the reference mol xyz into the 1-frame topologyTraj to use as a reference in the fit
setup_mol_array_coords = oechem.OEDoubleArray(3 *
set_up_flask.GetMaxAtomIdx())
set_up_flask.GetCoords(setup_mol_array_coords)
setup_mol_xyzArr = np.array(setup_mol_array_coords)
setup_mol_xyzArr.shape = (-1, 3)
trj_reference = trjImaged[0]
# convert from angstroms to nanometers
trj_reference.xyz[0] = setup_mol_xyzArr / 10.0
# Fitting
trjImaged.superpose(trj_reference, 0, ca_bs_idx)
# Delete Original Trajectory to save memory
del trj
# Molecule copies
ligand_reference = oechem.OEMol(ligand)
protein_reference = oechem.OEMol(protein)
count = 0
# Create the multi conformer protein, ligand and water molecules
for frame in trjImaged.xyz:
# print("Trj Image loop", count, flush=True)
# Extract coordinates in A
xyz = frame * 10
# Set flask Coordinates as the current frame for the water extraction
flask.SetCoords(xyz.flatten())
water_list_sorted_max = water_max_frames[count]
# print(water_list_sorted_max)
# TODO The following solution to extract the waters do not
# keep the water order
# Mark the close water atoms and extract them
bv = oechem.OEBitVector(nmax * 3)
water_idx = []
for pair in water_list_sorted_max:
ow = flask.GetAtom(oechem.OEHasAtomIdx(pair[0]))
# Select the whole water molecule
for atw in oechem.OEGetResidueAtoms(ow):
bv.SetBitOn(atw.GetIdx())
water_idx.append(atw.GetIdx())
pred_vec = oechem.OEAtomIdxSelected(bv)
water_nmax_reference = oechem.OEMol()
oechem.OESubsetMol(water_nmax_reference, flask, pred_vec)
# TODO The following solution to extract the waters
# keep the water order but is it seems extremely inefficient
# water_list = []
# for pair in water_list_sorted_max:
# bv = oechem.OEBitVector(3)
# water_idx = []
# ow = flask.GetAtom(oechem.OEHasAtomIdx(pair[0]))
#
# # Select the whole water molecule
# for atw in oechem.OEGetResidueAtoms(ow):
# bv.SetBitOn(atw.GetIdx())
# water_idx.append(atw.GetIdx())
#
# pred_vec = oechem.OEAtomIdxSelected(bv)
# water = oechem.OEMol()
# oechem.OESubsetMol(water, flask, pred_vec)
#
# water_list.append(water)
#
#
# # print(len(water_list))
#
# water_nmax_reference = oechem.OEMol()
# for w in water_list:
# oechem.OEAddMols(water_nmax_reference, w)
# ligand and protein conf coordinates
lig_xyz_list = [10 * frame[idx] for idx in lig_idx]
lig_confxyz = oechem.OEFloatArray(np.array(lig_xyz_list).ravel())
prot_xyz_list = [10 * frame[idx] for idx in prot_idx]
prot_confxyz = oechem.OEFloatArray(np.array(prot_xyz_list).ravel())
# Initialize the protein, ligand and water molecule topologies
if count == 0:
multi_conf_water = oechem.OEMol(water_nmax_reference)
if multi_conf_water.NumAtoms() % 3 != 0:
raise ValueError("Number of Water atoms is not multiple of 3")
# Clean ResNumber and Chain on the multi conf water molecule
# oechem.OEPerceiveResidues(multi_conf_water, oechem.OEPreserveResInfo_All)
multi_conf_water.SetTitle("Water_" + str(nmax))
res_num = 0
i = 0
for at in multi_conf_water.GetAtoms():
res = oechem.OEAtomGetResidue(at)
res.SetSerialNumber(i)
res.SetName("HOH")
res.SetChainID("Z")
if i % 3 == 0:
res_num += 1
res.SetResidueNumber(res_num)
i += 1
ligand_reference.SetCoords(lig_confxyz)
protein_reference.SetCoords(prot_confxyz)
multi_conf_ligand = oechem.OEMol(ligand_reference)
multi_conf_protein = oechem.OEMol(protein_reference)
# Attach the conformers on the multi conformer protein, ligand and water molecules
else:
water_confxyz = oechem.OEFloatArray(
water_nmax_reference.NumAtoms() * 3)
water_nmax_reference.GetCoords(water_confxyz)
multi_conf_water.NewConf(water_confxyz)
multi_conf_ligand.NewConf(lig_confxyz)
multi_conf_protein.NewConf(prot_confxyz)
count += 1
return multi_conf_protein, multi_conf_ligand, multi_conf_water