The FragmentLibrary implements a combinatorial library for reaction and reagent data. Its main task is to hold chemical information and provide new ligands. More...

#include <FragmentLibrary.hh>

Public Member Functions
	FragmentLibrary ()

	~FragmentLibrary ()

FragmentLibrary &	operator= (FragmentLibrary const &other)=delete

	FragmentLibrary (FragmentLibrary const &other)=delete

void	initialize_from_options (EvolutionOptionsOP options, core::Size external_scoring, core::Size rank)

void	set_pose (core::pose::PoseCOP pose)
	Sets the internally used pose for ligand creation. More...

core::pose::PoseOP	create_ligand_pose (LigandIdentifier const &id, bool create_rotamers, char ligand_chain) const
	generates a smiles representation for the id and calls create_ligand_pose with smiles More...

core::pose::PoseOP	create_ligand_pose (std::string const &smiles, bool create_rotamers, char ligand_chain) const
	generates a new residue represented by a given ligand code and adds it to a detached copy of the internally saved pose object More...

void	load_data (std::string const &reaction_file_path, std::string const &reagent_file_path, core::Size rank)
	Loads smirks reaction file and all reagents in the same folder. More...

void	load_smiles (std::string const &path_to_data)
	Loads external smiles for later scoring from file. More...

LigandIdentifier	random_ligand () const
	Simple function to generate a completely random ligand. More...

ReagentSimilarityList	get_similar_reagents (core::Size reagent_id, core::Size reaction_id, core::Size position) const
	Searches for similar reagents within a given reaction and position. More...

core::Size	reactions_size () const
	Returns the number of reactions. More...

core::Size	reagents_size () const
	Returns the total number of reagents. More...

core::Size	reagents_size (core::Size reaction_index) const
	Returns the total number of reagents for the given reaction. More...

core::Size	reagents_size (core::Size reaction_index, core::Size position) const
	Returns the number of reagents at one specific position in the given reaction. More...

core::Size	random_reaction () const
	Returns a random reaction index weighted for size of possible molecules. More...

core::Size	random_reaction (std::set< core::Size > const &exclude) const
	Returns a random reaction that is not included in exclude weighted for size of possible molecules. More...

std::string	reaction_id (core::Size reaction_id) const
	Returns the id of this reaction. More...

std::string	reagent_id (core::Size reagent_id) const
	Returns the id of this reagent. More...

std::string	run_reaction (LigandIdentifier const &identifier) const
	Runs the reaction specified by the ligand identifier and returns the resulting rdkit molecule. More...

std::string	identifier_to_smiles (LigandIdentifier const &identifier) const
	Generates a new molecule with rdkit reaction and returns its smiles representation. More...

core::Size	n_unscored_smiles () const
	Returns the number of saved external smiles that should be scored. More...

core::Size	max_positions () const
	Returns the number of maximum positions for all reactions used. More...

core::Size	reaction_positions (core::Size reaction_id) const
	Returns for a given reaction the number of positions used. More...

core::Size	reaction_name_to_index (std::string const &reaction_name) const
	Returns the used reaction index for a given reaction name. Returns 0 if not found. More...

core::Size	reagent_name_to_index (core::Size reaction_index, core::Size position, std::string const &reagent_name) const
	Returns the index for a given reagent. Returns 0 if not found. More...

std::shared_ptr< RDKit::SparseIntVect< unsigned int > >	calculate_fingerprint (LigandIdentifier const &id)
	Calculates a RDKit Morgan fingerprint for a given ligand. Fingerprints are saved and can be retrieved quickly. More...

core::Real	similarity (LigandIdentifier const &id1, LigandIdentifier const &id2)
	Returns the Tanimoto Similarity based on RDKit Morgan fingerprints for two given ligands. The fingerprints are either calculated or retrieved if previously calculated. More...

Private Member Functions
core::conformation::ResidueOP	create_ligand (std::string const &smiles, bool create_rotamers) const
	LigandIdentifier is interpreted as [reaction, reagent1, reagent2]. More...

void	load_reactions (std::string const &reaction_file_name)
	utility function to load all reactions. More...

void	load_reagents (std::string const &reagent_file_path)
	utility function to load all reagents. Returns indices of newly added entries in reagents_ More...

core::Size	generate_rotamers (core::chemical::MutableResidueType &new_ligand) const
	Tries to generate rotamers and returns how many were generated. More...

core::pose::PoseOP	create_pose (core::conformation::Residue &ligand, char ligand_chain) const
	Takes a ligand and adds it to a detached copy of the internally saved pose object. More...

Private Attributes
utility::vector1< ReagentOP >	reagents_
	List of all available reagents. More...

utility::vector1< ReactionOP >	reactions_
	List of all available reactions. More...

core::pose::PoseCOP	pose_
	Stores the original pose to dock all ligands in. More...

numeric::random::WeightedSampler	weighted_sampler_
	Weighted sampler for random unbiased selection. More...

utility::vector1< std::string >	smiles_
	Only used in benchmarking runs. Stores external molecules defined by smiles. More...

std::map< std::string, core::Size >	reaction_name_to_index_
	Used during data loading to map reaction names to indices whilst loading reagents. More...

core::Size	max_reagents_ = 0
	stores how many reagents are used at max for a reaction to set the correct length for ligand identifiers More...

std::map< LigandIdentifier, std::shared_ptr< RDKit::SparseIntVect< unsigned int > > >	fingerprints_
	stores calculated fingerprints for quick references More...

Detailed Description

The FragmentLibrary implements a combinatorial library for reaction and reagent data. Its main task is to hold chemical information and provide new ligands.

Constructor & Destructor Documentation

◆ FragmentLibrary() [1/2]

protocols::ligand_evolution::FragmentLibrary::FragmentLibrary ( )

default

◆ ~FragmentLibrary()

protocols::ligand_evolution::FragmentLibrary::~FragmentLibrary ( )

default

◆ FragmentLibrary() [2/2]

protocols::ligand_evolution::FragmentLibrary::FragmentLibrary ( FragmentLibrary const & other )

delete

Member Function Documentation

◆ calculate_fingerprint()

std::shared_ptr< RDKit::SparseIntVect< unsigned int > > protocols::ligand_evolution::FragmentLibrary::calculate_fingerprint ( LigandIdentifier const & id )

Calculates a RDKit Morgan fingerprint for a given ligand. Fingerprints are saved and can be retrieved quickly.

References fingerprints_, and run_reaction().

Referenced by similarity().

◆ create_ligand()

core::conformation::ResidueOP protocols::ligand_evolution::FragmentLibrary::create_ligand	(	std::string const &	smiles,
		bool	create_rotamers
	)		const

private

LigandIdentifier is interpreted as [reaction, reagent1, reagent2].

References core::chemical::rdkit::RDMolToRestype::generate_restype(), generate_rotamers(), core::chemical::ResidueType::make(), and protocols::TR().

Referenced by create_ligand_pose().

◆ create_ligand_pose() [1/2]

core::pose::PoseOP protocols::ligand_evolution::FragmentLibrary::create_ligand_pose	(	LigandIdentifier const &	id,
		bool	create_rotamers,
		char	ligand_chain
	)		const

generates a smiles representation for the id and calls create_ligand_pose with smiles

References run_reaction(), smiles_, and protocols::TR().

Referenced by protocols::ligand_evolution::Scorer::create_pose().

◆ create_ligand_pose() [2/2]

core::pose::PoseOP protocols::ligand_evolution::FragmentLibrary::create_ligand_pose	(	std::string const &	smiles,
		bool	create_rotamers,
		char	ligand_chain
	)		const

generates a new residue represented by a given ligand code and adds it to a detached copy of the internally saved pose object

References create_ligand(), create_pose(), and protocols::TR().

◆ create_pose()

core::pose::PoseOP protocols::ligand_evolution::FragmentLibrary::create_pose	(	core::conformation::Residue &	ligand,
		char	ligand_chain
	)		const

private

Takes a ligand and adds it to a detached copy of the internally saved pose object.

References protocols::sewing::data_storage::ligand, pose_, and protocols::TR().

Referenced by create_ligand_pose().

◆ generate_rotamers()

core::Size protocols::ligand_evolution::FragmentLibrary::generate_rotamers ( core::chemical::MutableResidueType & new_ligand ) const

private

Tries to generate rotamers and returns how many were generated.

References core::chemical::MutableResidueType::all_atoms(), core::chemical::MutableResidueType::atom_name(), core::chemical::AtomRefMapping< FromRef, ToRef >::invalid_entry(), core::chemical::rdkit::RestypeToRDMol::Mol(), core::chemical::MutableResidueType::nchi(), core::chemical::ResidueTypeBase::rotamer_library_specification(), protocols::TR(), and core::chemical::rdkit::RestypeToRDMol::vd_to_index().

Referenced by create_ligand().

◆ get_similar_reagents()

ReagentSimilarityList protocols::ligand_evolution::FragmentLibrary::get_similar_reagents	(	core::Size	reagent_id,
		core::Size	reaction_id,
		core::Size	position
	)		const

Searches for similar reagents within a given reaction and position.

References core::pose::motif::a(), protocols::match::upstream::b, reaction_id(), reactions_, reagent_id(), reagents_, and similarity().

Referenced by protocols::ligand_evolution::Crossover::cross(), and protocols::ligand_evolution::Mutator::mutate().

◆ identifier_to_smiles()

std::string protocols::ligand_evolution::FragmentLibrary::identifier_to_smiles ( LigandIdentifier const & identifier ) const

Generates a new molecule with rdkit reaction and returns its smiles representation.

References run_reaction(), and smiles_.

Referenced by protocols::ligand_evolution::Scorer::ligand_line(), and protocols::ligand_evolution::Scorer::save_external_scoring_results().

◆ initialize_from_options()

void protocols::ligand_evolution::FragmentLibrary::initialize_from_options	(	EvolutionOptionsOP	options,
		core::Size	external_scoring,
		core::Size	rank
	)

References load_data(), load_smiles(), and set_pose().

Referenced by protocols::ligand_evolution::EvolutionManager::init().

◆ load_data()

void protocols::ligand_evolution::FragmentLibrary::load_data	(	std::string const &	reaction_file_path,
		std::string const &	reagent_file_path,
		core::Size	rank
	)

Loads smirks reaction file and all reagents in the same folder.

References load_reactions(), load_reagents(), reactions_, reagents_, protocols::TR(), and weighted_sampler_.

Referenced by initialize_from_options().

◆ load_reactions()

void protocols::ligand_evolution::FragmentLibrary::load_reactions ( std::string const & reaction_file_name )

private

utility function to load all reactions.

References max_reagents_, reaction_name_to_index_, reactions_, and protocols::TR().

Referenced by load_data().

◆ load_reagents()

void protocols::ligand_evolution::FragmentLibrary::load_reagents ( std::string const & reagent_file_path )

private

utility function to load all reagents. Returns indices of newly added entries in reagents_

References reaction_name_to_index_, reactions_, reagents_, and protocols::TR().

Referenced by load_data().

◆ load_smiles()

void protocols::ligand_evolution::FragmentLibrary::load_smiles ( std::string const & path_to_data )

Loads external smiles for later scoring from file.

References smiles_, and protocols::TR().

Referenced by initialize_from_options().

◆ max_positions()

core::Size protocols::ligand_evolution::FragmentLibrary::max_positions ( ) const

Returns the number of maximum positions for all reactions used.

References max_reagents_.

Referenced by protocols::ligand_evolution::EvolutionManager::init_workmanager(), protocols::ligand_evolution::Scorer::ligand_line(), protocols::ligand_evolution::Scorer::load_scores(), and protocols::ligand_evolution::Scorer::save_results().

◆ n_unscored_smiles()

core::Size protocols::ligand_evolution::FragmentLibrary::n_unscored_smiles ( ) const

Returns the number of saved external smiles that should be scored.

References smiles_.

Referenced by protocols::ligand_evolution::EvolutionManager::external_scoring().

◆ operator=()

FragmentLibrary& protocols::ligand_evolution::FragmentLibrary::operator= ( FragmentLibrary const & other )

delete

◆ random_ligand()

LigandIdentifier protocols::ligand_evolution::FragmentLibrary::random_ligand ( ) const

Simple function to generate a completely random ligand.

References max_reagents_, random_reaction(), and reactions_.

Referenced by protocols::ligand_evolution::Population::add_random().

◆ random_reaction() [1/2]

core::Size protocols::ligand_evolution::FragmentLibrary::random_reaction ( ) const

Returns a random reaction index weighted for size of possible molecules.

References weighted_sampler_.

Referenced by protocols::ligand_evolution::Mutator::mutate(), and random_ligand().

◆ random_reaction() [2/2]

core::Size protocols::ligand_evolution::FragmentLibrary::random_reaction ( std::set< core::Size > const & exclude ) const

Returns a random reaction that is not included in exclude weighted for size of possible molecules.

References reactions_, and reactions_size().

◆ reaction_id()

std::string protocols::ligand_evolution::FragmentLibrary::reaction_id ( core::Size reaction_id ) const

Returns the id of this reaction.

References reactions_.

Referenced by protocols::ligand_evolution::Scorer::check_memory(), get_similar_reagents(), protocols::ligand_evolution::Scorer::ligand_line(), and reaction_positions().

◆ reaction_name_to_index()

core::Size protocols::ligand_evolution::FragmentLibrary::reaction_name_to_index ( std::string const & reaction_name ) const

Returns the used reaction index for a given reaction name. Returns 0 if not found.

References reaction_name_to_index_.

Referenced by protocols::ligand_evolution::Scorer::get_best_loaded().

◆ reaction_positions()

core::Size protocols::ligand_evolution::FragmentLibrary::reaction_positions ( core::Size reaction_id ) const

Returns for a given reaction the number of positions used.

References reaction_id(), and reactions_.

Referenced by protocols::ligand_evolution::Crossover::cross(), protocols::ligand_evolution::Scorer::ligand_line(), and protocols::ligand_evolution::Mutator::mutate().

◆ reactions_size()

core::Size protocols::ligand_evolution::FragmentLibrary::reactions_size ( ) const

Returns the number of reactions.

References reactions_.

Referenced by random_reaction().

◆ reagent_id()

std::string protocols::ligand_evolution::FragmentLibrary::reagent_id ( core::Size reagent_id ) const

Returns the id of this reagent.

References reagents_.

Referenced by protocols::ligand_evolution::Scorer::check_memory(), get_similar_reagents(), and protocols::ligand_evolution::Scorer::ligand_line().

◆ reagent_name_to_index()

core::Size protocols::ligand_evolution::FragmentLibrary::reagent_name_to_index	(	core::Size	reaction_index,
		core::Size	position,
		std::string const &	reagent_name
	)		const

Returns the index for a given reagent. Returns 0 if not found.

References reactions_, and reagents_.

Referenced by protocols::ligand_evolution::Scorer::get_best_loaded().

◆ reagents_size() [1/3]

core::Size protocols::ligand_evolution::FragmentLibrary::reagents_size ( ) const

Returns the total number of reagents.

References reagents_.

Referenced by protocols::ligand_evolution::Mutator::mutate(), and reagents_size().

◆ reagents_size() [2/3]

core::Size protocols::ligand_evolution::FragmentLibrary::reagents_size ( core::Size reaction_index ) const

Returns the total number of reagents for the given reaction.

References reactions_, and reagents_size().

◆ reagents_size() [3/3]

core::Size protocols::ligand_evolution::FragmentLibrary::reagents_size	(	core::Size	reaction_index,
		core::Size	position
	)		const

Returns the number of reagents at one specific position in the given reaction.

References reactions_.

◆ run_reaction()

std::string protocols::ligand_evolution::FragmentLibrary::run_reaction ( LigandIdentifier const & identifier ) const

Runs the reaction specified by the ligand identifier and returns the resulting rdkit molecule.

References reactions_, reagents_, and protocols::TR().

Referenced by calculate_fingerprint(), create_ligand_pose(), and identifier_to_smiles().

◆ set_pose()

void protocols::ligand_evolution::FragmentLibrary::set_pose ( core::pose::PoseCOP pose )

Sets the internally used pose for ligand creation.

References pose_.

Referenced by initialize_from_options().

◆ similarity()

core::Real protocols::ligand_evolution::FragmentLibrary::similarity	(	LigandIdentifier const &	id1,
		LigandIdentifier const &	id2
	)

Returns the Tanimoto Similarity based on RDKit Morgan fingerprints for two given ligands. The fingerprints are either calculated or retrieved if previously calculated.

References calculate_fingerprint().

Referenced by get_similar_reagents(), and protocols::ligand_evolution::Scorer::score_population().

Member Data Documentation

◆ fingerprints_

std::map< LigandIdentifier, std::shared_ptr< RDKit::SparseIntVect<unsigned int> > > protocols::ligand_evolution::FragmentLibrary::fingerprints_

private

stores calculated fingerprints for quick references

Referenced by calculate_fingerprint().

◆ max_reagents_

core::Size protocols::ligand_evolution::FragmentLibrary::max_reagents_ = 0

private

stores how many reagents are used at max for a reaction to set the correct length for ligand identifiers

Referenced by load_reactions(), max_positions(), and random_ligand().

◆ pose_

core::pose::PoseCOP protocols::ligand_evolution::FragmentLibrary::pose_

private

Stores the original pose to dock all ligands in.

Referenced by create_pose(), and set_pose().

◆ reaction_name_to_index_

std::map< std::string, core::Size > protocols::ligand_evolution::FragmentLibrary::reaction_name_to_index_

private

Used during data loading to map reaction names to indices whilst loading reagents.

Referenced by load_reactions(), load_reagents(), and reaction_name_to_index().

◆ reactions_

utility::vector1< ReactionOP > protocols::ligand_evolution::FragmentLibrary::reactions_

private

List of all available reactions.

Referenced by get_similar_reagents(), load_data(), load_reactions(), load_reagents(), random_ligand(), random_reaction(), reaction_id(), reaction_positions(), reactions_size(), reagent_name_to_index(), reagents_size(), and run_reaction().

◆ reagents_

utility::vector1< ReagentOP > protocols::ligand_evolution::FragmentLibrary::reagents_

private

List of all available reagents.

Referenced by get_similar_reagents(), load_data(), load_reagents(), reagent_id(), reagent_name_to_index(), reagents_size(), and run_reaction().

◆ smiles_

utility::vector1< std::string > protocols::ligand_evolution::FragmentLibrary::smiles_

private

Only used in benchmarking runs. Stores external molecules defined by smiles.

Referenced by create_ligand_pose(), identifier_to_smiles(), load_smiles(), and n_unscored_smiles().

◆ weighted_sampler_

numeric::random::WeightedSampler protocols::ligand_evolution::FragmentLibrary::weighted_sampler_

private

Weighted sampler for random unbiased selection.

Referenced by load_data(), and random_reaction().

The documentation for this class was generated from the following files:

src/protocols/ligand_evolution/FragmentLibrary.hh
src/protocols/ligand_evolution/FragmentLibrary.cc

Public Member Functions

Private Member Functions

Private Attributes

Detailed Description

Constructor & Destructor Documentation

◆ FragmentLibrary() [1/2]

◆ ~FragmentLibrary()

◆ FragmentLibrary() [2/2]

Member Function Documentation

◆ calculate_fingerprint()

◆ create_ligand()

◆ create_ligand_pose() [1/2]

◆ create_ligand_pose() [2/2]

◆ create_pose()

◆ generate_rotamers()

◆ get_similar_reagents()

◆ identifier_to_smiles()

◆ initialize_from_options()

◆ load_data()

◆ load_reactions()

◆ load_reagents()

◆ load_smiles()

◆ max_positions()

◆ n_unscored_smiles()

◆ operator=()

◆ random_ligand()

◆ random_reaction() [1/2]

◆ random_reaction() [2/2]

◆ reaction_id()

◆ reaction_name_to_index()

◆ reaction_positions()

◆ reactions_size()

◆ reagent_id()

◆ reagent_name_to_index()

◆ reagents_size() [1/3]

◆ reagents_size() [2/3]

◆ reagents_size() [3/3]

◆ run_reaction()

◆ set_pose()

◆ similarity()

Member Data Documentation

◆ fingerprints_

◆ max_reagents_

◆ pose_

◆ reaction_name_to_index_

◆ reactions_

◆ reagents_

◆ smiles_

◆ weighted_sampler_