#include <design.h>

Inheritance diagram for design:

Public Member Functions
	design (const char filename[], const char *const alphabet)
	Constructor. Programmer provides a filename for a ct file. More...

int	design_sequence (double &pernucdefect, const bool random, const int maxdepth=5, bool heuristic=false, int MaxRedesignC=10, int MaxMutateC=4, int MaxLeafRedesignC=3, long randomSeed=1L)

void	SpecifyRedesignLimits (int leaf, int parent, int mutate)

void	SpecifyWeightedDefect (bool DefectWeighted)

Public Member Functions inherited from RNA
	RNA (const char sequence[], const bool IsRNA=true)
	Constructor - user provides a sequence as a c string. More...

	RNA (const char filepathOrSequence[], const RNAInputType fileType, const char *const alphabetName, const bool allowUnknownBases=false, const bool skipThermoTables=false)

	RNA (const char filepathOrSequence[], const RNAInputType fileType, const Thermodynamics *copyThermo)

	RNA (const char filename[], const RNAInputType fileType, const bool IsRNA=true)
	Constructor - user provides a filename for existing file as a c string. More...

	RNA (const bool IsRNA=true)

int	GetErrorCode () const
	Return an error code, where a return of zero is no error. More...

string	GetFullErrorMessage () const

const string	GetErrorDetails () const
	Returns extended details about the last error. (e.g. error messages produced during file read operations that are otherwise lost.) More...

void	SetErrorDetails (const string &details)
	Set extended details about the last error. (e.g. error messages produced during file read operations that are otherwise lost.) More...

string	GetErrorMessageString (const int error) const
	Return error messages based on code from GetErrorCode and other error codes. More...

void	ResetError ()

void	EnsureStructureCapcacity (const int minimumStructures)
	Ensure that at a minumum number of structures have been created. More...

int	SpecifyPair (const int i, const int j, const int structurenumber=1)
	Specify a base pair between nucleotides i and j. More...

int	RemovePairs (const int structurenumber=1, bool removeIfLastStructure=true)
	Remove all the current base pairs in a specified structure. More...

int	RemoveBasePair (const int i, const int structurenumber=1)
	Remove a specified pair in a specified structure. More...

double	CalculateFreeEnergy (const int structurenumber=1, const bool UseSimpleMBLoopRules=false)
	Return the predicted Gibb's free energy change for structure # structurenumber, defaulted to 1. More...

int	WriteThermodynamicDetails (const char filename[], const bool UseSimpleMBLoopRules=false)
	Calculate the folding free energy change for all structures and write the details of the calculation to a file. More...

int	FoldSingleStrand (const float percent=20, const int maximumstructures=20, const int window=5, const char savefile[]="", const int maxinternalloopsize=30, bool mfeonly=false, bool simple_iloops=true, bool disablecoax=false)
	Predict the lowest free energy secondary structure and generate suboptimal structures using a heuristic. More...

int	GenerateAllSuboptimalStructures (const float percent=5, const double deltaG=0.6)
	Predict the lowest free energy secondary structure and generate all suboptimal structures. More...

int	MaximizeExpectedAccuracy (const double maxPercent=20, const int maxStructures=20, const int window=1, const double gamma=1.0)
	Predict the structure with maximum expected accuracy and suboptimal structures. More...

int	PartitionFunction (const char savefile[]="", double temperature=-10.0, bool disablecoax=false, bool restoreSHAPE=true)
	Predict the partition function for a sequence. More...

int	Rsample (const vector< double > &experimentalRestraints, RsampleData &refdata, const int randomSeed=0, const char savefile[]="", const double cparam=0.5, const double offset=1.10, const int numsamples=10000)

int	PredictProbablePairs (const float probability=0)
	Predict structures containing highly probable pairs. More...

int	ProbKnot (int iterations=1, int MinHelixLength=1)
	Predict maximum expected accuracy structures that contain pseudoknots from either a sequence or a partition function save file. More...

int	ProbKnotFromSample (int iterations=1, int MinHelixLength=1)
	Predict maximum expected accuracy structures that contain pseudoknots from a file containing ensemble of structures. More...

int	ReFoldSingleStrand (const float percent=20, const int maximumstructures=20, const int window=5)
	Re-predict the lowest free energy secondary structure and generate suboptimal structures using a heuristic. More...

int	Stochastic (const int structures=1000, const int seed=1)
	Sample structures from the Boltzman ensemable. More...

int	ForceDoubleStranded (const int i)
	Force a nucleotide to be double stranded (base paired). More...

int	ForceFMNCleavage (const int i)
	Indicate a nucleotide that is accessible to FMN cleavage (a U in GU pair). More...

int	ForceMaximumPairingDistance (const int distance)
	Force a maximum distance between apired nucleotides. More...

int	ForceModification (const int i)
	Force modification for a nucleotide. More...

int	ForcePair (const int i, const int j)
	Force a pair between two nucleotides. More...

int	ForceProhibitPair (const int i, const int j)
	Prohibit a pair between two nucleotides. More...

int	ForceSingleStranded (const int i)
	Force a nucleotide to be single stranded. More...

int	GetForcedDoubleStranded (const int constraintnumber)
	Return a nucleotide that is forced double stranded. More...

int	GetForcedFMNCleavage (const int constraintnumber)
	Return a nucleotide that is accessible to FMN cleavage. More...

int	GetForcedModification (const int constraintnumber)
	Return a nucleotide that is accessible to modification. More...

int	GetForcedPair (const int constraintnumber, const bool fiveprime)
	Return a nucleotide in a forced pair. More...

int	GetForcedProhibitedPair (const int constraintnumber, const bool fiveprime)
	Return a nucleotide in a prohibited pair. More...

int	GetForcedSingleStranded (const int constraintnumber)
	Return a nucleotide that is forced single stranded. More...

int	GetMaximumPairingDistance ()
	Return the maximum pairing distance. More...

int	GetNumberOfForcedDoubleStranded ()
	Return the number of nucletides forced to be paired. More...

int	GetNumberOfForcedFMNCleavages ()
	Return the number of nucleotides accessible to FMN cleavage. More...

int	GetNumberOfForcedModifications ()
	Return the number of nucleotides accessible to chemical modification. More...

int	GetNumberOfForcedPairs ()
	Return the number of forced base pairs. More...

int	GetNumberOfForcedProhibitedPairs ()
	Return the number of prohibited base pairs. More...

int	GetNumberOfForcedSingleStranded ()
	Return the number of nucleotides that are not allowed to pair. More...

int	ReadConstraints (const char filename[])
	Read a set of folding constraints to disk in a plain text file. More...

int	ReadSHAPE (const char filename[], const double slope, const double intercept, RestraintType modifier=RESTRAINT_SHAPE, const bool IsPseudoEnergy=true)
	Read SHAPE data from disk. More...

int	ReadSHAPE (const char filename[], const double dsSlope, const double dsIntercept, const double ssSlope, const double ssIntercept, RestraintType modifier=RESTRAINT_SHAPE)
	Read SHAPE data from disk including single-stranded SHAPE pseudo free energys. More...

int	ReadDMS (const char filename[])

int	ReadDSO (const char filename[])
	Read double strand offset data from disk. More...

int	ReadSSO (const char filename[])
	Read single strand offset data from disk. More...

int	ReadExperimentalPairBonus (const char filename[], double const experimentalOffset, double const experimentalScaling)
	Read experimental pair bonuses from disk. More...

void	RemoveConstraints ()
	Remove all folding constraints. More...

int	SetExtrinsic (int i, int j, double k)
	Add extrinsic restraints for partition function calculations. More...

int	WriteConstraints (const char filename[])
	Write the current set of folding constraints to disk in a plain text file. More...

int	AddComment (const char comment[], const int structurenumber=1)
	Add a comment associated with a structure. More...

int	WriteCt (const char filename[], bool append=false, const CTCommentProvider &commentProvider=DEFAULT_CT_ENERGY_COMMENTS) const
	Write a ct file of the structures. More...

int	WriteDotBracket (const char filename[], const int structurenumber=-1, const DotBracketFormat format=DBN_FMT_MULTI_TITLE, const CTCommentProvider &commentProvider=DEFAULT_CT_ENERGY_COMMENTS) const
	Write dot-bracket file of structures. More...

int	BreakPseudoknot (const bool minimum_energy=true, const int structurenumber=0, const bool useFastMethod=true)
	Break any pseudoknots that might be in a structure. More...

bool	ContainsPseudoknot (const int structurenumber)
	Report if there are any pseudoknots in a structure. More...

double	GetEnsembleEnergy ()
	Get the ensemble folding free energy change. More...

double	GetEnsembleDefect (const int structurenumber=1)
	Get the ensemble defect of a secondary structure. More...

double	GetFreeEnergy (const int structurenumber)
	Get the folding free energy change for a predicted structure. More...

int	GetPair (const int i, const int structurenumber=1)
	Get the nucleotide to which the specified nucleotide is paired. More...

double	GetPairEnergy (const int i, const int j)
	Get the lowest folding free energy possible for a structure containing pair i-j. More...

double	GetPairProbability (const int i, const int j)
	Get a base pair probability. More...

int	GetPairProbabilities (double *arr, const int size)

int	GetStructureNumber () const
	Get the total number of specified or predicted structures. More...

int	DetermineDrawingCoordinates (const int height, const int width, const int structurenumber=1)
	Determine the coordinates for drawing a secondary structure. More...

std::string	GetCommentString (const int structurenumber=1)
	Provide the comment from the ct file as a string. More...

int	GetNucleotideXCoordinate (const int i)
	Get the X coordinate for nucleotide i for drawing a structure. More...

int	GetNucleotideYCoordinate (const int i)
	Get the Y coordinate for nucleotide i for drawing a structure. More...

int	GetLabelXCoordinate (const int i)
	Get the X coordinate for placing the nucleotide index label specified by i. More...

int	GetLabelYCoordinate (const int i)
	Get the Y coordinate for placing the nucleotide index label specified by i. More...

char	GetNucleotide (const int i)

int	GetSequenceLength () const
	Get the total length of the sequence. More...

const char *	GetSequence ()

bool	GetBackboneType () const
	Get the backbone type. More...

structure *	GetStructure ()

void	SetProgress (ProgressHandler &Progress)

void	StopProgress ()

ProgressHandler *	GetProgress ()

	~RNA ()
	Destructor. More...

Public Member Functions inherited from Thermodynamics
	Thermodynamics (const bool isRNA=true, const char *const alphabetName=NULL, const double temperature=310.15)

	Thermodynamics (const Thermodynamics &copyThermo)

int	SetTemperature (double temperature)
	Set the temperature of folding in K. More...

double	GetTemperature () const

string	GetAlphabetName () const
	Get the name of the extended alphabet for which thermodynamic parameters should be loaded. More...

int	ReadThermodynamic (const char directory=NULL, const char alphabet=NULL, const double temperature=-1.0)
	Function to read the thermodynamic parameters. More...

int	ReloadDataTables (const double new_temperature=-1.0)

bool	VerifyThermodynamic ()
	Force the datatables to be read if they haven't already. Return true if the tables were already loaded or if the attempt to (re)open them succeded. More...

datatable *	GetDatatable ()

datatable *	GetEnthalpyTable (const char *alphabet=NULL)

void	ClearEnergies ()
	Copy thermodynamic parameters from an instance of Thermodynamics class. More...

void	ClearEnthalpies ()
	Clear the currently loaded enthalpy datatable and release its resources. More...

bool	GetEnergyRead () const
	Return whether this instance of Thermodynamics has the paremters populated (either from disk or from another Thermodynamics class). More...

bool	IsAlphabetRead () const

	~Thermodynamics ()

Private Member Functions
void	decompose (int nucstart, int nucend, int currentdepth, int maxdepth, int **tree, int missingstart=0, int missingend=0)

bool	closeenoughtocut (int i, int j, int nucstart, int nucend, int missingstart, int missingend, double CLOSENESS)

void	marktree (int beststart, int bestend, int nucstart, int nucend, int missingstart, int missingend, int currentdepth, int **tree)

void	bestdecomposition (int nuctstart, int nucend, int currentstart, int currentend, int beststart, int bestend, int missingstart, int missingend)

double	SelectSequence (int **tree, bool random, int depth, const double pernucdefect, long seed=1)

double	SelectSequenceHeuristic (int **tree, bool random, int depth, const double pernucdefect, long seed=1)

void	FindFragments (int *tree, int level, int start, int stop, int missingstart, int missingstop, vector< int > stackstart, vector< int > stackend, vector< int > stackmissingstart, vector< int > stackmissingend, vector< int > stackfragmentdepth)

void	FillSequence (int start, int end, int missingstart, int missingend, bool random, randomnumber *dice, vector< vector< string > > &Helices, vector< vector< string > > &Loops)

int	MapNuctoFragment (int j, int start, int missingstart, int missingend)

int	MapFragmenttoNuc (int j, int start, int missingstart, int missingend)

void	Mutation (int maxDefPos, int start, int missingstart, int missingend, char *sequence, vector< int > &Mutated)

void	GetDefect (int start, int end, int missingstart, int missingend, vector< double > &def, double &defect, RNA *fragment)

void	Debug1 (int start, int end, int missingstart, int missingend, char sequence, RNA fragment)

void	PlaceSeqOnStack (vector< int > stackstart, vector< int > stackend, vector< int > stackmissingstart, vector< int > stackmissingend, vector< int > *stackfragmentdepth)

void	StoreMutation (int start, int end, int missingstart, int missingend, char *sequence)

void	StoreBestSequence (int start, int end, int missingstart, int missingend, char **sequence, int fragmentdepth)

char	tonuc (int i)

int	toint (char i)

double	leafdesign (int start, int end, int missingstart, int missingend, bool random, randomnumber dice, vector< vector< string > > Helices, vector< vector< string > > Loops, double pernucdefect, Thermodynamics thermo)

void	LeafOptimize (const double pernucdefect, randomnumber &dice, double &defect, vector< double > &def, RNA fragment, int start, int end, int missingstart, int missingend, char sequence, Thermodynamics *thermo)

Private Attributes
int	MaxRedesign

int	MaxMutate

int	MaxLeafRedesign

bool	defectweighted

int	numbering

Additional Inherited Members
Static Public Member Functions inherited from RNA
static const char *	GetErrorMessage (const int error)
	Return error messages based on code from GetErrorCode and other error codes. More...

Public Attributes inherited from Thermodynamics
bool	isrna

Protected Member Functions inherited from RNA
int	FileReader (const char filename[], const RNAInputType fileType)

Protected Attributes inherited from RNA
int	ErrorCode

ProgressHandler *	progress

PFPRECISION *	w5

PFPRECISION *	w3

PFPRECISION **	wca

pfdatatable *	pfdata

DynProgArray< PFPRECISION > *	w

DynProgArray< PFPRECISION > *	v

DynProgArray< PFPRECISION > *	wmb

DynProgArray< PFPRECISION > *	wl

DynProgArray< PFPRECISION > *	wmbl

DynProgArray< PFPRECISION > *	wcoax

PFPRECISION	Q

Protected Attributes inherited from Thermodynamics
datatable *	data

datatable *	enthalpy

bool	copied

double	nominal_temperature

string	nominal_alphabetName

bool	skipThermoTables

Constructor & Destructor Documentation

design::design	(	const char	filename[],
		const char *const	alphabet
	)

Constructor. Programmer provides a filename for a ct file.

Read a ct with name filename. This is a template for the structure. The sequence in the ct file will be ignored. If IsRNA is true (default), this is RNA, and it is DNA otherwise.

Parameters

filename	is a null terminated cstring that provides the filename and path.
alphabet	is c-string that specifies the alphabet (e.g. rna, dna, or custom)

Member Function Documentation

void design::bestdecomposition	(	int	nuctstart,
		int	nucend,
		int	currentstart,
		int	currentend,
		int *	beststart,
		int *	bestend,
		int	missingstart,
		int	missingend
	)

private

bool design::closeenoughtocut	(	int	i,
		int	j,
		int	nucstart,
		int	nucend,
		int	missingstart,
		int	missingend,
		double	CLOSENESS
	)

private

void design::Debug1	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		char *	sequence,
		RNA *	fragment
	)

private

void design::decompose	(	int	nucstart,
		int	nucend,
		int	currentdepth,
		int	maxdepth,
		int **	tree,
		int	missingstart = `0`,
		int	missingend = `0`
	)

private

int design::design_sequence	(	double &	pernucdefect,
		const bool	random,
		const int	maxdepth = `5`,
		bool	heuristic = `false`,
		int	MaxRedesignC = `10`,
		int	MaxMutateC = `4`,
		int	MaxLeafRedesignC = `3`,
		long	randomSeed = `1L`
	)

Design the sequence. This function will choose a sequence with low ensemble defect to fold to the structure read in the constructor. The sequence is stored in the underlying RNA class.

Parameters

pernucdefect	is the maximum allowed ensemble defect per nucleotide.
random	determines the method for choosing sequence. If false, use pre-selected sequences, and otherwise (true), randomly choose the sequence.
maxdepth	is the maximum extent to which the structure will be sub-divided in the binary decomposition. The default is 5.
heuristic	if true, avoids performing a partition function on the complete sequence. Default is false.
MaxRedesignC	specifies the maximum number of redesigns.
MaxMutateC	is the maximum number of nucleotide mutations to make.
MaxLeafRedesignC	is the maximum number of time a leaf will be redesigned when building the tree.
randomSeed	is the seed for the random number generator.

Returns: An int error code that can be resolved to a message using RNA::GetErrorMessage. A return of 0 means no errors.

void design::FillSequence	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		bool	random,
		randomnumber *	dice,
		vector< vector< string > > &	Helices,
		vector< vector< string > > &	Loops
	)

private

void design::FindFragments	(	int **	tree,
		int	level,
		int	start,
		int	stop,
		int	missingstart,
		int	missingstop,
		vector< int > *	stackstart,
		vector< int > *	stackend,
		vector< int > *	stackmissingstart,
		vector< int > *	stackmissingend,
		vector< int > *	stackfragmentdepth
	)

private

void design::GetDefect	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		vector< double > &	def,
		double &	defect,
		RNA *	fragment
	)

private

end else, (j!=missingstart)

double design::leafdesign	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		bool	random,
		randomnumber *	dice,
		vector< vector< string > > *	Helices,
		vector< vector< string > > *	Loops,
		double	pernucdefect,
		Thermodynamics *	thermo
	)

private

void design::LeafOptimize	(	const double	pernucdefect,
		randomnumber &	dice,
		double &	defect,
		vector< double > &	def,
		RNA *	fragment,
		int	start,
		int	end,
		int	missingstart,
		int	missingend,
		char *	sequence,
		Thermodynamics *	thermo
	)

private

int design::MapFragmenttoNuc	(	int	j,
		int	start,
		int	missingstart,
		int	missingend
	)

private

int design::MapNuctoFragment	(	int	j,
		int	start,
		int	missingstart,
		int	missingend
	)

private

void design::marktree	(	int	beststart,
		int	bestend,
		int	nucstart,
		int	nucend,
		int	missingstart,
		int	missingend,
		int	currentdepth,
		int **	tree
	)

private

void design::Mutation	(	int	maxDefPos,
		int	start,
		int	missingstart,
		int	missingend,
		char *	sequence,
		vector< int > &	Mutated
	)

private

void design::PlaceSeqOnStack	(	vector< int > *	stackstart,
		vector< int > *	stackend,
		vector< int > *	stackmissingstart,
		vector< int > *	stackmissingend,
		vector< int > *	stackfragmentdepth
	)

private

double design::SelectSequence	(	int **	tree,
		bool	random,
		int	depth,
		const double	pernucdefect,
		long	seed = `1`
	)

private

defect<=pernucdefect

double design::SelectSequenceHeuristic	(	int **	tree,
		bool	random,
		int	depth,
		const double	pernucdefect,
		long	seed = `1`
	)

private

void design::SpecifyRedesignLimits	(	int	leaf,
		int	parent,
		int	mutate
	)

Change the defaults for maximum redesigns. This function allows the programmer to change the maximum number of redesigns at three levels from the defaults. The defaults are to redesign leaves (leaf) up to 3 times, parent nodes (parent) up to 10 times, and to mutate nucleotides for defect-weighted mutation (mutate) up to 4 times.

Parameters

leaf	is an int that specifies the maximum number of times the leaf is re-optimized at random.
parent	is an int that specifies the maximum number of redesigns per parent node.
mutate	is an int that specifies the maximum number of times a nucleotide will be mutated during defect-weighted reoptimization.

void design::SpecifyWeightedDefect ( bool DefectWeighted )

Change the default for whether weighted-defect optimization should occur. This function allows the programmer to change whether the ascent back up the tree (if check of weighted defect fails) should only redesign a fraction of the sequence. The default is for this to occur.

Parameters

DefectWeighted is a bool that specifies whether defect-weighted re-optimization should occur (true=yes, false=no).

void design::StoreBestSequence	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		char **	sequence,
		int	fragmentdepth
	)

private

void design::StoreMutation	(	int	start,
		int	end,
		int	missingstart,
		int	missingend,
		char *	sequence
	)

private

int design::toint ( char i )

private

char design::tonuc ( int i )

private

Member Data Documentation

bool design::defectweighted

private

int design::MaxLeafRedesign

private

int design::MaxMutate

private

int design::MaxRedesign

private

int design::numbering

private

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

RNA_class/design.h
RNA_class/design.cpp

Public Member Functions

Private Member Functions

Private Attributes

Additional Inherited Members

Constructor & Destructor Documentation

Member Function Documentation

Member Data Documentation