schrodinger.application.pathfinder.multiroute module

Functions to support multi-route enumeration (AKA “simple reaction enumeration” or “automated reaction enumeration”).

class schrodinger.application.pathfinder.multiroute.MultiRouteEnumerator(mol, *, reactions_dict=None, dedup=True, depth=None, descriptors='MolLogP, MolWt, NumChiralCenters, NumHAcceptors, NumHDonors, TPSA', frozen_atoms=frozenset({}), libpath=None, max_per_route=1000, max_routes=100, no_core_hopping=False, product_property_filter_file=None, product_smarts_filter_file=None, ref_mols=None, ch_dist_tol=1.0, ch_ang_tol=15.0, bond_reactions=None, prefilter_reagents=None, fp_dir=None, fp_url=None, fp_namespace=None, forward=False, prng=<module 'random' from '/scr/buildbot/savedbuilds/2024-4/NB/build-117/internal/lib/python3.11/random.py'>, route_prng=None, **unused_args)

Bases: object

A generator of products following the multiroute enumeration protocol.

__init__(mol, *, reactions_dict=None, dedup=True, depth=None, descriptors='MolLogP, MolWt, NumChiralCenters, NumHAcceptors, NumHDonors, TPSA', frozen_atoms=frozenset({}), libpath=None, max_per_route=1000, max_routes=100, no_core_hopping=False, product_property_filter_file=None, product_smarts_filter_file=None, ref_mols=None, ch_dist_tol=1.0, ch_ang_tol=15.0, bond_reactions=None, prefilter_reagents=None, fp_dir=None, fp_url=None, fp_namespace=None, forward=False, prng=<module 'random' from '/scr/buildbot/savedbuilds/2024-4/NB/build-117/internal/lib/python3.11/random.py'>, route_prng=None, **unused_args)
Parameters

  • mol (rdkit.Chem.Mol) – input molecule to be used for the initial retrosynthetic or forward analysis.

  • dedup (bool) – skip duplicate products (using SMILES for comparison)

  • depth (int or NoneType) – analysis depth (if None, increasing depths will be attempted until enough routes are found)

  • descriptors (list of str) – names of RDKit descriptors to compute for each product

  • frozen_atoms (set of int) – indexes (1-based) of atoms to keep in the product

  • libpath (list of str) – directories to search for reactant files

  • max_per_route (int) – maximum number of products per route

  • max_routes (int) – maximum number of routes to sample

  • no_core_hopping (bool) – don’t use the special core hopping mode even when possible

  • product_property_filter_file (str) – name of JSON file with product property filters

  • product_smarts_filter_file (str) – name of .cflt file with SMARTS patterns

  • ref_mols (list(Mol) or str) – reference molecules for similarity calculations

  • ch_dist_tol (float) – core-hopping distance tolerance in Angstroms (maximum allowed change in the distance between side chains, relative to the input structure)

  • ch_ang_tol (float) – core-hopping angle tolerance in degrees (maximum change bond vector angle for side chains, relative to the input structure)

  • bond_reactions – dict specifying which reactions are allowed to break certain bonds. Keys are tuples of two ints (sorted atom indexes); values are sets of reaction names.

  • bond_reactions – {(int, int): set(str)}

  • prefilter_reagents (int or NoneType) – number of most similar molecules to return.

  • fp_dir (str or NoneType) – directory to search for fingerprint files in addition to CWD

  • forward (bool) – use forward analysis mode (routes start from mol instead of ending there)

  • prng (random.Random) – pseudo-random number generator to be used for the enumeration, for picking the route and reactants to try at each iteration

  • route_prng (random.Random or NoneType) – pseudo-random number generator to be used for selecting the subset of routes to use, based on max_routes. If not supplied, prng will be used.

generate_mols()
Return type

generator of Mol

schrodinger.application.pathfinder.multiroute.get_fp_file(reactant_file, cache_dir, url_base=None, subdir='')

Get a fingerprint file for a given reactant file. First look at the cache dir; if not found, and a URL is supplied, try to download it from the server and write it to the cache dir.

For a reactant file named foo.pfx, the fingerprint file must be named foo-<sha1>.fp, where <sha1> is the SHA1 hash of foo.pfx.

Parameters

  • reactant_file (str) – reactant file for which we are looking for fingerprints

  • cache_dir (str) – local directory where fingerprint files are/will be stored

Url_base

base URL to try to download fingerprint files from

Subdir

optionally, subdirectory of cache_dir and URL to use

Returns

path to fingerprint file, if found; else None

Return type

str or NoneType

schrodinger.application.pathfinder.multiroute.download_and_decompress(url, dest)

GET a gzip-compressed file from a URL and write it out, decompressed to the local filesystem. The contents are first downloaded to a temporary file and then renamed atomically. A locking mechanism is employed to try to prevent concurrent downloads of the same file.

Parameters

  • url (str) – URL to download

  • dest (str) – destination filename

Returns

dest if successful, else None (e.g. in case of 404)

Return type

str or NoneType

schrodinger.application.pathfinder.multiroute.get_fp_basename(reactant_file)

Return the basename of the fingerprint file corresponding to the given reactant file, following the convention that for a reactant file named foo.pfx, the fingerprint file must be named foo-<sha1>.fp, where <sha1> is the SHA1 hash of foo.pfx.

Parameters

reactant_file (str) – reactant file

Returns

basename of fingerprint file

Return type

str

schrodinger.application.pathfinder.multiroute.get_sha1(filename)

Return the SHA1 hash of a file.

Parameters

filename (str) – input file

Returns

hex SHA1 digest of file contents

Return type

str

schrodinger.application.pathfinder.multiroute.get_lock(basename, max_wait, interval=1.0)

Create a <basename>.lock file on entry and remove it on exit. If the file already exists, wait up to max_wait seconds for the lock to clear. If the timeout is exceeded, assume that the lock is stale and ignore it.

This is a very rudimentary mechanism, but is good enough for the purposes of this module, which is just to _try_ to prevent simultaneous downloads of the same file, but where occasional collisions don’t hurt beyond the slight waste of bandwith and temporary use of disk space.

Parameters

  • basename (str) – basename of lock file

  • max_wait (float) – maximum wait in seconds

  • interval (float) – time to sleep between attempts, in seconds

Returns

context manager that removes lock file on exit

Return type

contextlib._GeneratorContextManager

schrodinger.application.pathfinder.multiroute.has_variable_reactants(route)

Check if the route has at least one variable reactant.

Parameters

route (schrodinger.application.pathfinder.route.RouteNode) – route to analyze

Returns

does the route have at least one variable reactant?

Return type

bool

schrodinger.application.pathfinder.multiroute.is_core_sm(sm, core_atoms)

Check if a starting material node corresponds to a core.

Parameters
Return type

bool

schrodinger.application.pathfinder.multiroute.meta_sample(samples, dedup=True, prng=<module 'random' from '/scr/buildbot/savedbuilds/2024-4/NB/build-117/internal/lib/python3.11/random.py'>)

A generator that, on each cycle, picks a random element of samples and yields the next element from said sample. It never stops unless all samples raise StopIteration.

Each product gets annotated with properties representing the route that was used to make the molecule.

Parameters

  • samples (list of iterator of Mol) – molecule samples

  • dedup (bool) – skip duplicate products

  • prng (random.Random) – pseudo-random number generator

Returns

molecule generator

Return type

generator of rdkit.Chem.Mol

schrodinger.application.pathfinder.multiroute.measure_vectors(st, r1, c1, r2, c2)

Measure the distance and angle between two bond vectors. The distance is measured between atoms r1 and r2; the angle is between the c1-r1 and c2-r2 vectors.

Parameters

  • st (schrodinger.structure.Structure) – structure to measure

  • r1 (int) – R-group attachment atom 1

  • c1 (int) – core atom 1

  • r2 (int) – R-group attachment atom 2

  • c2 (int) – core atom 2

Returns

distance and angle

Return type

float, float

schrodinger.application.pathfinder.multiroute.st_from_mol(mol)

Convert a Mol into a Structure, with 3D coordinates but no added hydrogens. Missing stereochemistry is tolerated.

Parameters

mol (rdkit.Chem.rdchem.Mol) – molecule

Returns

Structure

Return type

schrodinger.structure.Structure

schrodinger.application.pathfinder.multiroute.is_core(graph, free_component, frozen_components)

Check if the free_component subgraph should be considered a core, meaning that it is connected to more than one of the free_components.

Parameters

  • graph (networkx.classes.graph.Graph) – molecular graph

  • free_component (set of int) – possible core atom indices

  • frozen_components (list of set of int) – possible sidechain atom indexes

Returns

is it a core?

Return type

bool

schrodinger.application.pathfinder.multiroute.apply_similarity_filters(products, args)

Implement the -sim_keep_percent and -sim_discard_percent functionality.

Parameters

  • products (iterator of rdkit.Chem.Mol) – molecules to filter

  • args (argparse.Namespace) – command-line arguments

Returns

filtered products and number of products to keep

Return type

generator of rdkit.Chem.Mol, int

schrodinger.application.pathfinder.multiroute.analyze_frozen_atoms(mol, frozen_atoms)

Examine the molecular graph of the input molecule to partition it, based on the set of frozen atoms, into free regions and frozen regions. Also determine which free region is the core, if any.

A core in this context is a contiguous set of non-frozen atoms which is adjacent to two or more sets of frozen atoms (the side chains).

Jobs with two or more cores will abort immediately.

When there is a core, also measure the distances and angles between all the pairs of vectors leading from the core to the side chains. The resulting dict has pairs of atoms as keys, and (distance, angle) tuples as values.

In addition to the set of core atoms, a set of “core neighbors” is also returned. These are the non-core atoms that are directly connected to the core.

Parameters

  • mol (rdkit.Chem.rdchem.Mol) – input molecule

  • frozen_atoms (set of int) – frozen atom indices

Returns

measurements, core atoms, core neighbors

Return type

dict {(int, int): (float, float)}, set of int, set of int

schrodinger.application.pathfinder.multiroute.generate_mols(*a, **d)

A generator of products following the multiroute enumeration protocol.

This is a thin functional wrapper around the MultiRouteEnumerator class. For arguments, see MultiRouteEnumerator.__init__.

Return type

generator of Mol

schrodinger.application.pathfinder.multiroute.write_products(products, filename, max_products, has_frozen_atoms=False)

Write out up to max_products from a mol iterator to a file.

Parameters

  • products (iterator of Mol) – molecules to write

  • filename (str) – filename

  • max_products (int) – maximum number of structures to write

  • has_frozen_atoms (bool) – True if user specified frozen atoms

schrodinger.application.pathfinder.multiroute.get_output_writer(align_products, filename)

If we’re generating maestro structures (.mae, mae.gz, .maegz we need to generate structures, align, them, and then write them out. If not, we can write products out with the MolWriter.

Parameters

args (argparse.Namespace) – input arguments used to create the output sink

Align_products

flag indicating product alignment