List of parameters¶

Parameters for version 1.2.0¶

Genetic Algorithm parameters

population (int): size of the starting population, in number of individuals. Default: 12
generations (int): number of generations to simulate. Default: 500
mu (float): the number of children to select at each generation, expressed as a multiplier of ga.population. Default: 1
lambda_ (float): the number of children to produce at each generation, expressed as a multiplier of ga.population. Default: 1.0
mut_eta (float): crowding degree of the mutation. A high eta will produce a mutant resembling its parent, while a small eta will produce a solution much more different. Default: 5
mut_pb (float): the probability that an offspring is produced by mutation. Default: 0.8
mut_indpb (float): independent probability for each gene to be mutated. Default: 1.0
cx_eta (float): crowding degree of the crossover. A high eta will produce children resembling to their parents, while a small eta will produce solutions much more different. Default: 5
cx_pb (float): the probability that an offspring is produced by crossover. Default: 0.2

Path gene

radius_rotamers (float): Maximum distance (in Angstroms) from any point of the ligand in every frame that is searched for possible rotamers of the protein side-chain. Default: 3.0
max_step_separation (float): Maximum distance (in Angstroms) from one point of the ligand in the pathway to the next one. If not set by the user, GPathFinder calculates the value from the size of the ligand. Default: None
min_step_increment (float): Minimum distance increment (in Angstroms) from the ligand’s origin that has to be the ligand in one frame of the pathway with respect of the ligand’s distance from the origin of the previous frame of the pathway. If not set by the user, GPathFinder calculates the value as 2/5 by max_step_separation. Default: None
mut_pos_pb (float): When a mutation occurs, this value is the probability of such mutation to be of the type positions, that is, the mutation changes the actual trajectory of the pathway. Warning: parameter for advanced users, usually the default value is correct for the vast majority of the systems. Default: 0.10

Path_torsion gene

flexibility (int or float): Maximum number of degrees a bond can rotate. Default: 360.0
anchor (str): Molecule/atom_serial_number of reference atom for torsions. If not set, the nearest atom to the molecule geometric center is selected. Default: None
rotatable_atom_types (list of str): Which type of atom types (as in chimera.Atom.idatmType) should rotate. Default: (‘C3’, ‘N3’, ‘C2’, ‘N2’, ‘P’)
rotatable_atom_names (list of str): Which type of atom names (as in chimera.Atom.name) should rotate. Default: ()
non_rotatable_bonds (list of str): Which bonds (identified by [Molecule/SerialNumber1, Molecule/SerialNumber2]) are not allowed to rotate. Default: ()
non_rotatable_selection (str): Which bonds (identified by a Chimera selection query) are not allowed to rotate. Default: ()

Path_rotamers gene

library {‘Dunbrack’, ‘Dynameomics’}: The rotamer library to use. Default: Dunbrack

Path_normalmodes gene

method {‘prody’, ‘gaussian’, ‘pca’}: prody to calculate normal modes using prody algorithms, gaussian to read normal modes from a gaussian output file and pca to perform a PCA analysis over a MD trajectory (.dcd file). Default: prody
modes (list of int): Modes to be used to move the molecule. Default: [0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
pca_atoms {‘calpha’, ‘backbone’, ‘all’}: which atoms of the receptor are selected in the PCA analysis. Default: calpha
group_by {‘residues’, ‘mass’, ‘calpha’, ‘’}: method to group atoms when using a coarse grain model of the receptor. Default: residues
group_lambda (int): Either number of residues per group (default=15), or total mass per group (default=100)
n_samples (int): number of conformations to generate. Default: 100
rmsd (float): average RMSD, in Angstroms, that conformations will have with respect to the initial conformation. Default: 2.0
minimize (bool): whether to minimize the resulting samples or not. Default: False
forcefields (list of str): Used when minimize is True to indicate which forcefields to use. It can be a .prmtop file containing the parametrization and topology of the Protein. Default: (‘amber99sbildn.xml’,)
minimization_tolerance (float): used when minimize is True. Convergence criteria for energy minimization. In kJ/mol. Default: 10.0
minimization_iterations (int): used when minimize is True. Max attempts to converge at minimization. Default: 1000

Path_scoring objective

radius (float): maximum distance, in Angstroms, from any point of the ligand in every frame that is searched for possible interactions. Default: 5.0
method {‘sum’, ‘average’, ‘max’}: Method used to calculate the score (i.e. sum, average or maximum of the scores of all frames). Default: average
clash_threshold (float): used when the scoring is clashes. Maximum overlap of van-der-Waals spheres. If the overlap is greater, it’s considered a clash. Default: 0.6
bond_separation (int): used when the scoring is clashes. Ignore clashes between atoms within n bonds. Default: 4
same_residue (bool): used when the scoring is clashes. Include intra-molecular clashes. Default: True
smoothness_threshold (float): used when method is smoothness. RMSD between ligands on two consecutive frames that is permitted considering a perfect score of smoothness. Default: 0.0
smina_scoring (str): used when the scoring is smina to specify alternative builtin scoring function (e.g. vinardo). Default: None
smina_custom_scoring (str): used when the scoring is smina to specify a custom scoring function file. Default: None
smina_custom_atoms (str): used when the scoring is smina to specify a custom atom type parameters file. Default: None

Parameters for version 1.1.0¶

Genetic Algorithm parameters

population (int): size of the starting population, in number of individuals. Default: 12
generations (int): number of generations to simulate. Default: 500
mu (float): the number of children to select at each generation, expressed as a multiplier of ga.population. Default: 1
lambda_ (float): the number of children to produce at each generation, expressed as a multiplier of ga.population. Default: 1.0
mut_eta (float): crowding degree of the mutation. A high eta will produce a mutant resembling its parent, while a small eta will produce a solution much more different. Default: 5
mut_pb (float): the probability that an offspring is produced by mutation. Default: 0.8
mut_indpb (float): independent probability for each gene to be mutated. Default: 1.0
cx_eta (float): crowding degree of the crossover. A high eta will produce children resembling to their parents, while a small eta will produce solutions much more different. Default: 5
cx_pb (float): the probability that an offspring is produced by crossover. Default: 0.2

Path gene

radius_rotamers (float): Maximum distance (in Angstroms) from any point of the ligand in every frame that is searched for possible rotamers of the protein side-chain. Default: 3.0
max_step_separation (float): Maximum distance (in Angstroms) from one point of the ligand in the pathway to the next one. If not set by the user, GPathFinder calculates the value from the size of the ligand. Default: None
min_step_increment (float): Minimum distance increment (in Angstroms) from the ligand’s origin that has to be the ligand in one frame of the pathway with respect of the ligand’s distance from the origin of the previous frame of the pathway. If not set by the user, GPathFinder calculates the value as 2/5 by max_step_separation. Default: None
mut_pos_pb (float): When a mutation occurs, this value is the probability of such mutation to be of the type positions, that is, the mutation changes the actual trajectory of the pathway. Warning: parameter for advanced users, usually the default value is correct for the vast majority of the systems. Default: 0.10

Path_torsion gene

flexibility (int or float): Maximum number of degrees a bond can rotate. Default: 360.0
anchor (str): Molecule/atom_serial_number of reference atom for torsions. If not set, the nearest atom to the molecule geometric center is selected. Default: None
rotatable_atom_types (list of str): Which type of atom types (as in chimera.Atom.idatmType) should rotate. Default: (‘C3’, ‘N3’, ‘C2’, ‘N2’, ‘P’)
rotatable_atom_names (list of str): Which type of atom names (as in chimera.Atom.name) should rotate. Default: ()
non_rotatable_bonds (list of str): Which bonds (identified by [Molecule/SerialNumber1, Molecule/SerialNumber2]) are not allowed to rotate. Default: ()
non_rotatable_selection (str): Which bonds (identified by a Chimera selection query) are not allowed to rotate. Default: ()

Path_rotamers gene

library {‘Dunbrack’, ‘Dynameomics’}: The rotamer library to use. Default: Dunbrack

Path_normalmodes gene

method {‘prody’, ‘gaussian’}: prody to calculate normal modes using prody algorithms and gaussian to read normal modes from a gaussian output file. Default: prody
modes (list of int): Modes to be used to move the molecule. Default: [0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
group_by {‘residues’, ‘mass’, ‘calpha’, ‘’}: method to group atoms when using a coarse grain model of the receptor. Default: residues
group_lambda (int): Either number of residues per group (default=15), or total mass per group (default=100)
n_samples (int): number of conformations to generate. Default: 100
rmsd (float): average RMSD, in Angstroms, that conformations will have with respect to the initial conformation. Default: 2.0
minimize (bool): whether to minimize the resulting samples or not. Default: False
forcefields (list of str): Used when minimize is True to indicate which forcefields to use. It can be a .prmtop file containing the parametrization and topology of the Protein. Default: (‘amber99sbildn.xml’,)
minimization_tolerance (float): used when minimize is True. Convergence criteria for energy minimization. In kJ/mol. Default: 10.0
minimization_iterations (int): used when minimize is True. Max attempts to converge at minimization. Default: 1000

Path_scoring objective

radius (float): maximum distance, in Angstroms, from any point of the ligand in every frame that is searched for possible interactions. Default: 5.0
method {‘sum’, ‘average’, ‘max’}: Method used to calculate the score (i.e. sum, average or maximum of the scores of all frames). Default: average
clash_threshold (float): used when the scoring is clashes. Maximum overlap of van-der-Waals spheres. If the overlap is greater, it’s considered a clash. Default: 0.6
bond_separation (int): used when the scoring is clashes. Ignore clashes between atoms within n bonds. Default: 4
same_residue (bool): used when the scoring is clashes. Include intra-molecular clashes. Default: True
smoothness_threshold (float): used when method is smoothness. RMSD between ligands on two consecutive frames that is permitted considering a perfect score of smoothness. Default: 0.0
smina_scoring (str): used when the scoring is smina to specify alternative builtin scoring function (e.g. vinardo). Default: None
smina_custom_scoring (str): used when the scoring is smina to specify a custom scoring function file. Default: None
smina_custom_atoms (str): used when the scoring is smina to specify a custom atom type parameters file. Default: None

Parameters for versions 1.0.x¶

Genetic Algorithm parameters

population (int): size of the starting population, in number of individuals. Default: 12
generations (int): number of generations to simulate. Default: 500
mu (float): the number of children to select at each generation, expressed as a multiplier of ga.population. Default: 1
lambda_ (float): the number of children to produce at each generation, expressed as a multiplier of ga.population. Default: 1.0
mut_eta (float): crowding degree of the mutation. A high eta will produce a mutant resembling its parent, while a small eta will produce a solution much more different. Default: 5
mut_pb (float): the probability that an offspring is produced by mutation. Default: 0.8
mut_indpb (float): independent probability for each gene to be mutated. Default: 1.0
cx_eta (float): crowding degree of the crossover. A high eta will produce children resembling to their parents, while a small eta will produce solutions much more different. Default: 5
cx_pb (float): the probability that an offspring is produced by crossover. Default: 0.2

Path gene

radius_rotamers (float): Maximum distance (in Angstroms) from any point of the ligand in every frame that is searched for possible rotamers of the protein side-chain. Default: 3.0
max_step_separation (float): Maximum distance (in Angstroms) from one point of the ligand in the pathway to the next one. If not set by the user, GPathFinder calculates the value from the size of the ligand. Default: None
min_step_increment (float): Minimum distance increment (in Angstroms) from the ligand’s origin that has to be the ligand in one frame of the pathway with respect of the ligand’s distance from the origin of the previous frame of the pathway. If not set by the user, GPathFinder calculates the value as 2/5 by max_step_separation. Default: None
mut_pos_pb (float): When a mutation occurs, this value is the probability of such mutation to be of the type positions, that is, the mutation changes the actual trajectory of the pathway. Warning: parameter for advanced users, usually the default value is correct for the vast majority of the systems. Default: 0.10

Path_torsion gene

flexibility (int or float): Maximum number of degrees a bond can rotate. Default: 360.0
anchor (str): Molecule/atom_serial_number of reference atom for torsions. If not set, the nearest atom to the molecule geometric center is selected. Default: None
rotatable_atom_types (list of str): Which type of atom types (as in chimera.Atom.idatmType) should rotate. Default: (‘C3’, ‘N3’, ‘C2’, ‘N2’, ‘P’)
rotatable_atom_names (list of str): Which type of atom names (as in chimera.Atom.name) should rotate. Default: ()
non_rotatable_bonds (list of str): Which bonds (identified by [Molecule/SerialNumber1, Molecule/SerialNumber2]) are not allowed to rotate. Default: ()
non_rotatable_selection (str): Which bonds (identified by a Chimera selection query) are not allowed to rotate. Default: ()

Path_rotamers gene

library {‘Dunbrack’, ‘Dynameomics’}: The rotamer library to use. Default: Dunbrack

Path_normalmodes gene

method {‘prody’, ‘gaussian’}: prody to calculate normal modes using prody algorithms and gaussian to read normal modes from a gaussian output file. Default: prody
modes (list of int): Modes to be used to move the molecule. Default: [0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
group_by {‘residues’, ‘mass’, ‘calpha’, ‘’}: method to group atoms when using a coarse grain model of the receptor. Default: residues
group_lambda (int): Either number of residues per group (default=15), or total mass per group (default=100)
n_samples (int): number of conformations to generate. Default: 100
rmsd (float): average RMSD, in Angstroms, that conformations will have with respect to the initial conformation. Default: 2.0
minimize (bool): whether to minimize the resulting samples or not. Default: False
forcefields (list of str): Used when minimize is True to indicate which forcefields to use. It can be a .prmtop file containing the parametrization and topology of the Protein. Default: (‘amber99sbildn.xml’,)
minimization_tolerance (float): used when minimize is True. Convergence criteria for energy minimization. In kJ/mol. Default: 10.0
minimization_iterations (int): used when minimize is True. Max attempts to converge at minimization. Default: 1000

Path_scoring objective

radius (float): maximum distance, in Angstroms, from any point of the ligand in every frame that is searched for possible interactions. Default: 5.0
method {‘sum’, ‘average’, ‘max’}: Method used to calculate the score (i.e. sum, average or maximum of the scores of all frames). Default: average
clash_threshold (float): used when the scoring is clashes. Maximum overlap of van-der-Waals spheres. If the overlap is greater, it’s considered a clash. Default: 0.6
bond_separation (int): used when the scoring is clashes. Ignore clashes between atoms within n bonds. Default: 4
same_residue (bool): used when the scoring is clashes. Include intra-molecular clashes. Default: True
smoothness_threshold (float): used when method is smoothness. RMSD between ligands on two consecutive frames that is permitted considering a perfect score of smoothness. Default: 0.0