def test_process(self):
amber_relax = relax.AmberRelaxation(**self.test_config)
with open(os.path.join(self.test_dir, 'model_output.pdb')) as f:
test_prot = protein.from_pdb_string(f.read())
pdb_min, debug_info, num_violations = amber_relax.process(prot=test_prot)
self.assertCountEqual(debug_info.keys(),
set({'initial_energy', 'final_energy',
'attempts', 'rmsd'}))
self.assertLess(debug_info['final_energy'], debug_info['initial_energy'])
self.assertGreater(debug_info['rmsd'], 0)
prot_min = protein.from_pdb_string(pdb_min)
# Most protein properties should be unchanged.
np.testing.assert_almost_equal(test_prot.aatype, prot_min.aatype)
np.testing.assert_almost_equal(test_prot.residue_index,
prot_min.residue_index)
# Atom mask and bfactors identical except for terminal OXT of last residue.
np.testing.assert_almost_equal(test_prot.atom_mask[:-1, :],
prot_min.atom_mask[:-1, :])
np.testing.assert_almost_equal(test_prot.b_factors[:-1, :],
prot_min.b_factors[:-1, :])
np.testing.assert_almost_equal(test_prot.atom_mask[:, :-1],
prot_min.atom_mask[:, :-1])
np.testing.assert_almost_equal(test_prot.b_factors[:, :-1],
prot_min.b_factors[:, :-1])
# There are no residues with violations.
np.testing.assert_equal(num_violations, np.zeros_like(num_violations))
def test_to_pdb(self):
with open(
os.path.join(absltest.get_default_test_srcdir(), TEST_DATA_DIR,
'2rbg.pdb')) as f:
pdb_string = f.read()
prot = protein.from_pdb_string(pdb_string, chain_id='A')
pdb_string_reconstr = protein.to_pdb(prot)
prot_reconstr = protein.from_pdb_string(pdb_string_reconstr)
np.testing.assert_array_equal(prot_reconstr.aatype, prot.aatype)
np.testing.assert_array_almost_equal(prot_reconstr.atom_positions,
prot.atom_positions)
np.testing.assert_array_almost_equal(prot_reconstr.atom_mask,
prot.atom_mask)
np.testing.assert_array_equal(prot_reconstr.residue_index,
prot.residue_index)
np.testing.assert_array_almost_equal(prot_reconstr.b_factors,
prot.b_factors)
def test_from_pdb_str(self, pdb_file, chain_id, num_res):
pdb_file = os.path.join(absltest.get_default_test_srcdir(),
TEST_DATA_DIR, pdb_file)
with open(pdb_file) as f:
pdb_string = f.read()
prot = protein.from_pdb_string(pdb_string, chain_id)
self._check_shapes(prot, num_res)
self.assertGreaterEqual(prot.aatype.min(), 0)
# Allow equal since unknown restypes have index equal to restype_num.
self.assertLessEqual(prot.aatype.max(), residue_constants.restype_num)
def test_unresolved_violations(self):
amber_relax = relax.AmberRelaxation(**self.test_config)
with open(os.path.join(self.test_dir,
'with_violations_casp14.pdb')) as f:
test_prot = protein.from_pdb_string(f.read())
_, _, num_violations = amber_relax.process(prot=test_prot)
exp_num_violations = np.array(
[0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0, 1, 1, 1, 1, 1, 1,
1, 1, 1, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 1, 1, 1, 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0,
0, 0, 0, 0])
# Check no violations were added. Can't check exactly due to stochasticity.
self.assertTrue(np.all(num_violations <= exp_num_violations))
def test_ideal_atom_mask(self):
with open(
os.path.join(absltest.get_default_test_srcdir(), TEST_DATA_DIR,
'2rbg.pdb')) as f:
pdb_string = f.read()
prot = protein.from_pdb_string(pdb_string, chain_id='A')
ideal_mask = protein.ideal_atom_mask(prot)
non_ideal_residues = set([102] + list(range(127, 285)))
for i, (res,
atom_mask) in enumerate(zip(prot.residue_index,
prot.atom_mask)):
if res in non_ideal_residues:
self.assertFalse(np.all(atom_mask == ideal_mask[i]),
msg=f'{res}')
else:
self.assertTrue(np.all(atom_mask == ideal_mask[i]),
msg=f'{res}')
def test_overwrite_b_factors(self):
testdir = os.path.join(
absltest.get_default_test_srcdir(),
'alphafold/relax/testdata/'
'multiple_disulfides_target.pdb')
with open(testdir) as f:
test_pdb = f.read()
n_residues = 191
bfactors = np.stack([np.arange(0, n_residues)] * 37, axis=-1)
output_pdb = utils.overwrite_b_factors(test_pdb, bfactors)
# Check that the atom lines are unchanged apart from the B-factors.
atom_lines_original = [l for l in test_pdb.split('\n') if l[:4] == ('ATOM')]
atom_lines_new = [l for l in output_pdb.split('\n') if l[:4] == ('ATOM')]
for line_original, line_new in zip(atom_lines_original, atom_lines_new):
self.assertEqual(line_original[:60].strip(), line_new[:60].strip())
self.assertEqual(line_original[66:].strip(), line_new[66:].strip())
# Check B-factors are correctly set for all atoms present.
as_protein = protein.from_pdb_string(output_pdb)
np.testing.assert_almost_equal(
np.where(as_protein.atom_mask > 0, as_protein.b_factors, 0),
np.where(as_protein.atom_mask > 0, bfactors, 0))
def _load_test_protein(data_path):
pdb_path = os.path.join(absltest.get_default_test_srcdir(), data_path)
with open(pdb_path, 'r') as f:
return protein.from_pdb_string(f.read())
def run_pipeline(
prot: protein.Protein,
stiffness: float,
max_outer_iterations: int = 1,
place_hydrogens_every_iteration: bool = True,
max_iterations: int = 0,
tolerance: float = 2.39,
restraint_set: str = "non_hydrogen",
max_attempts: int = 100,
checks: bool = True,
exclude_residues: Optional[Sequence[int]] = None):
"""Run iterative amber relax.
Successive relax iterations are performed until all violations have been
resolved. Each iteration involves a restrained Amber minimization, with
restraint exclusions determined by violation-participating residues.
Args:
prot: A protein to be relaxed.
stiffness: kcal/mol A**2, the restraint stiffness.
max_outer_iterations: The maximum number of iterative minimization.
place_hydrogens_every_iteration: Whether hydrogens are re-initialized
prior to every minimization.
max_iterations: An `int` specifying the maximum number of L-BFGS steps
per relax iteration. A value of 0 specifies no limit.
tolerance: kcal/mol, the energy tolerance of L-BFGS.
The default value is the OpenMM default.
restraint_set: The set of atoms to restrain.
max_attempts: The maximum number of minimization attempts per iteration.
checks: Whether to perform cleaning checks.
exclude_residues: An optional list of zero-indexed residues to exclude from
restraints.
Returns:
out: A dictionary of output values.
"""
# `protein.to_pdb` will strip any poorly-defined residues so we need to
# perform this check before `clean_protein`.
_check_residues_are_well_defined(prot)
pdb_string = clean_protein(prot, checks=checks)
exclude_residues = exclude_residues or []
exclude_residues = set(exclude_residues)
violations = np.inf
iteration = 0
while violations > 0 and iteration < max_outer_iterations:
ret = _run_one_iteration(
pdb_string=pdb_string,
exclude_residues=exclude_residues,
max_iterations=max_iterations,
tolerance=tolerance,
stiffness=stiffness,
restraint_set=restraint_set,
max_attempts=max_attempts)
prot = protein.from_pdb_string(ret["min_pdb"])
if place_hydrogens_every_iteration:
pdb_string = clean_protein(prot, checks=True)
else:
pdb_string = ret["min_pdb"]
ret.update(get_violation_metrics(prot))
ret.update({
"num_exclusions": len(exclude_residues),
"iteration": iteration,
})
violations = ret["violations_per_residue"]
exclude_residues = exclude_residues.union(ret["residue_violations"])
logging.info("Iteration completed: Einit %.2f Efinal %.2f Time %.2f s "
"num residue violations %d num residue exclusions %d ",
ret["einit"], ret["efinal"], ret["opt_time"],
ret["num_residue_violations"], ret["num_exclusions"])
iteration += 1
return ret