schrodinger.livedesign.biologics.registration module¶

This file serves as the primary entry point for Live Design biologics. In particular, it provides an API for: (1) Converting user input data into a canonical data structure for storage and database manipulation. (2) Computing a default set of properties and descriptors.

class schrodinger.livedesign.biologics.registration.MoleculeClass(value)¶

Bases: enum.Enum

An enumeration.

CHEM = 1¶

DNA = 2¶

RNA = 3¶

PEPTIDE = 4¶

ANTIBODY_LIGHT_FV = 5¶

ANTIBODY_LIGHT_FAB = 6¶

ANTIBODY_HEAVY_FV = 7¶

ANTIBODY_HEAVY_FAB = 8¶

ANTIBODY_HEAVY_FAB_PRIME = 9¶

ANTIBODY_HEAVY_FULL = 10¶

FV = 11¶

FAB = 12¶

ANTIBODY_ARM_FULL = 13¶

ANTIBODY_ARM_FAB_PRIME = 14¶

FAB2 = 15¶

MONOSPECIFIC_ANTIBODY = 16¶

BISPECIFIC_ANTIBODY = 17¶

COMPLEX = 18¶

class schrodinger.livedesign.biologics.registration.RegistrationDescriptors(average_molecular_weight, exact_molecular_weight, total_charge, molecular_formula)¶

Bases: tuple

average_molecular_weight: float¶: Alias for field number 0

exact_molecular_weight: float¶: Alias for field number 1

total_charge: int¶: Alias for field number 2

molecular_formula: str¶: Alias for field number 3

__contains__(key, /)¶: Return key in self.

__len__()¶: Return len(self).

count(value, /)¶: Return number of occurrences of value.

index(value, start=0, stop=9223372036854775807, /)¶

Return first index of value.

Raises ValueError if the value is not present.

class schrodinger.livedesign.biologics.registration.RegistrationData(canonicalized_helm, requested_hash, child_hashes, bio_class)¶

Bases: tuple

canonicalized_helm: str¶: Alias for field number 0

requested_hash: str¶: Alias for field number 1

child_hashes: List[str]¶: Alias for field number 2

bio_class: schrodinger.livedesign.biologics.registration.MoleculeClass¶: Alias for field number 3

__contains__(key, /)¶: Return key in self.

__len__()¶: Return len(self).

count(value, /)¶: Return number of occurrences of value.

index(value, start=0, stop=9223372036854775807, /)¶

Return first index of value.

Raises ValueError if the value is not present.

class schrodinger.livedesign.biologics.registration.BioPolymer(polymer_id: str, monomer_string: str, bio_class: schrodinger.livedesign.biologics.registration.MoleculeClass, requested_hash: int, connections: Set[ForwardRef('BioPolymer')] = <factory>, neighbors: Set[ForwardRef('BioPolymer')] = <factory>)¶

Bases: object

polymer_id: str¶

monomer_string: str¶

bio_class: schrodinger.livedesign.biologics.registration.MoleculeClass¶

requested_hash: int¶

connections: Set[schrodinger.livedesign.biologics.registration.BioPolymer]¶

neighbors: Set[schrodinger.livedesign.biologics.registration.BioPolymer]¶

addConnection(neighbor: schrodinger.livedesign.biologics.registration.BioPolymer)¶: Instead of tracking inter-polymer connections directly, maintain a connection list to find non-self neighbors.

__init__(polymer_id: str, monomer_string: str, bio_class: schrodinger.livedesign.biologics.registration.MoleculeClass, requested_hash: int, connections: Set[schrodinger.livedesign.biologics.registration.BioPolymer] = <factory>, neighbors: Set[schrodinger.livedesign.biologics.registration.BioPolymer] = <factory>) → None¶

schrodinger.livedesign.biologics.registration.biologic_registration_process(helm_str: str) → Iterator[schrodinger.livedesign.biologics.registration.RegistrationData]¶

Primary entrypoint for LiveDesign Biologics data digestion.

Given an input HELM string, returns the following: (1) The RegistrationData of the full helm model defined by the string (2) RegistrationData for each large oligomeric subunit (e.g. the antibody in an antibody-drug conjugate) (3) RegistrationData for each simple polymer

Notably, this function uses the Bioluminate antibody detection modules to detect antibody sequences and classify all HELM protein chains (“peptides”) into their respective antibody class, if any, and then combines the antibody chains into well-defined larger constructs.

Parameters: helm_str – input HELM string. Assumed to be a connected collection of simple polymers, with no disconnected subunits.
Returns: an iterator over the hierachy of biologic entities in increasing complexity. For example, an antibody-drug conjugate would return: 1. antibody heavy and light chains 2. a small moelcule 3. the arms of the antibody 4. the antibody 5. the antibody-drug conjugate

schrodinger.livedesign.biologics.registration.extract_registration_data(polymer: schrodinger.protein.helm._helm_parser.HelmPolymer, helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → schrodinger.livedesign.biologics.registration.RegistrationData¶

Helper function to extract the connectivity metadata and the Registration data for a particular polymer from given helm model.

Parameters

polymer – the helm polymer to extract, in RegistrationData format
helm_model – the helm model to extract the RegistrationData from

Returns

the RegistrationData instance for the polymer

schrodinger.livedesign.biologics.registration.build_polymer_graph(connections: Iterable[schrodinger.protein.helm._helm_parser.HelmConnection], polymer_dict: Dict[str, schrodinger.livedesign.biologics.registration.BioPolymer]) → None¶

Simple function to store neighbors as a list in each BioPolymer instead of storing connections, in order to explore polymer neighborhoods efficiently.

Parameters

connections – list of HelmConnections defining the BioPolymer graph
polymer_dict – the dictionary of BioPolymers for easy BioPolymer management

schrodinger.livedesign.biologics.registration.find_antibodies(polymers: List[schrodinger.livedesign.biologics.registration.BioPolymer], helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → List[schrodinger.livedesign.biologics.registration.RegistrationData]¶

Find and classify all contiguous antibody polymer combinations if connectivity is provided, otherwise just assemble them into one large antibody.

Parameters

polymers – list of BioPolymers to search for antibodies
helm_model – source HelmModel, used to generate new HelmModels

Returns

a list of RegistrationData for each found antibody construct

schrodinger.livedesign.biologics.registration.is_antibody_subunit(bio_class: schrodinger.livedesign.biologics.registration.MoleculeClass) → bool¶: Utility function to increase readability.

schrodinger.livedesign.biologics.registration.find_abs_by_connectivity(polymer_graph: List[schrodinger.livedesign.biologics.registration.BioPolymer], helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → List[schrodinger.livedesign.biologics.registration.RegistrationData]¶

Depth-first search approach to finding all directly connected antibody components in a helm polymer network.

Parameters

helm_model – source helm model to query for connectivity and extract HelmPolymers from for output subunits
polymer_graph – the list of all BioPolymers

Returns

a list of RegistrationData for each found (and recognized) antibody constructs

schrodinger.livedesign.biologics.registration.find_ab_chain(biopolymer: schrodinger.livedesign.biologics.registration.BioPolymer, used_polymers: Set[schrodinger.livedesign.biologics.registration.BioPolymer]) → List[schrodinger.livedesign.biologics.registration.BioPolymer]¶

Recursive function to grow an antibody chain from one polymer to reach all reachable antibody fragments.

Parameters: used_polymers – the set of “seen” polymers to avoid infinite recursion

schrodinger.livedesign.biologics.registration.create_combined_ab_data(ab_polymer_chain: List[schrodinger.livedesign.biologics.registration.BioPolymer], helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → schrodinger.livedesign.biologics.registration.RegistrationData¶

Given a set of BioPolymers, extract them from the given helm_model and create a new RegistrationData object consisting only of the set.

Parameters

ab_polymer_chain – the collection of antibody Biopolymers to combine
helm_model – the source helm_model containing connections and HelmPolymer objects to extract

Returns

the RegistrationData of the final combined object

schrodinger.livedesign.biologics.registration.classify_ab_assembly(ab_polymer_chain: List[schrodinger.livedesign.biologics.registration.BioPolymer]) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

Given a bunch of antibodies, find a matching, recognized antibody construct and return it.

Parameters: ab_polymer_chain – the chain of connected antibody subunuits
Returns: the overall antibody class the collective subunits create, if any

schrodinger.livedesign.biologics.registration.get_arm_data(ab_polymer_chain: List[schrodinger.livedesign.biologics.registration.BioPolymer], helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → Iterable[schrodinger.livedesign.biologics.registration.RegistrationData]¶

Given a list of connected BioPolymers, find the arms (light/heavy pairs) and return the registration data for each arm. Each arm must be from a F(ab’)2, monospecific antibody, or bispecific antibody. An arm thus consists of a light Fab domain, connected to a heavy full or heavy Fab’ chain. The heavy chain can connect to other heavy chains, but two light chains sharing a heavy chain would not fall into any of the currently supported classes.

Parameters

ab_polymer_chain – the full set of connected antibody chains
helm_model – source helm model to extract helm strings and connections from.

Returns

generator over the available arms in the antibody polymer chain.

schrodinger.livedesign.biologics.registration.postprocess_registration_data(data: schrodinger.livedesign.biologics.registration.RegistrationData) → schrodinger.livedesign.biologics.registration.RegistrationData¶: Postprocessing step for subunit RegistrationData. Currently just remove duplicate child hashes.

schrodinger.livedesign.biologics.registration.replace_base_chains(subunit: schrodinger.livedesign.biologics.registration.RegistrationData, child_hashes: List[str], hash_dict: Dict[str, schrodinger.livedesign.biologics.registration.RegistrationData]) → None¶

Helper function to recursively traverse the set of returned RegistrationData and replace base chain data with their combined subunit in the top-level child hash list.

Parameters

child_hashes – top-level hash list
hash_dict – all returned child hashes so far
subunit – the current subunit to insert into child_hashes

schrodinger.livedesign.biologics.registration.get_serialized_representation(canonical_helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → str¶

Externally available serialization API for HELM serialization.

Parameters: canonical_helm_model – canonicalized helm model
Returns: a HELM string

schrodinger.livedesign.biologics.registration.get_requested_hash(canonical_helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → int¶

Unified HELM model hasher for biologics registration

Parameters: canonicalized_helm_model – a HelmModel to hash
Returns: sha1 hashed HELM string.

schrodinger.livedesign.biologics.registration.combine_helm(biopolymers: List[schrodinger.livedesign.biologics.registration.BioPolymer], helm_model: schrodinger.protein.helm._helm_parser.HelmModel) → schrodinger.protein.helm._helm_parser.HelmModel¶

Function to ensure recombined HELM strings always canonicalize the same way. Sometimes indistinguishable simple polymers (other than who they’re connected to) can get swapped, changing the connection section and the resulting final hash.

Parameters: biopolymers – BioPolymer instances whose corresponding polymers will be extracted
Returns: a HelmModel consisting only of the specified biopolymers

schrodinger.livedesign.biologics.registration.light_heavy_heavy_light(light_chains: List[schrodinger.livedesign.biologics.registration.BioPolymer], heavy_chains: List[schrodinger.livedesign.biologics.registration.BioPolymer]) → bool¶

Ensure that the connectivity is light-heavy-heavy-light, which correspondes to a full antibody.

Parameters

light_chains – the list of connected light chains
heavy_chains – the list of connected heavy chains

schrodinger.livedesign.biologics.registration.is_deoxyribose(helm_monomer: schrodinger.protein.helm._helm_parser.HelmMonomer) → bool¶

schrodinger.livedesign.biologics.registration.is_standard_ribose(helm_monomer: schrodinger.protein.helm._helm_parser.HelmMonomer) → bool¶

schrodinger.livedesign.biologics.registration.classify_polymer(helm_polymer: schrodinger.protein.helm._helm_parser.HelmPolymer) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

Given a HelmPolymer (a polymer consisting of only one type), infer its type.

Parameters: helm_polymer – helm_polymer to determine class of

schrodinger.livedesign.biologics.registration.classify_nucleotide_polymer(helm_polymer) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

schrodinger.livedesign.biologics.registration.classify_protein(helm_polymer) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

schrodinger.livedesign.biologics.registration.classify_antibody(helm_polymer, ab_classification) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

schrodinger.livedesign.biologics.registration.classify_overall_molecule(polymer_chains: List[schrodinger.livedesign.biologics.registration.BioPolymer]) → schrodinger.livedesign.biologics.registration.MoleculeClass¶

Given a collection of polymers, return the corresponding MoleculeClass.

Parameters: polymer_chains – the set of polymers to classify