Python-based
Hierarchical
ENvironment
for
Integrated
Xtallography
Contents
Nigel W. Moriarty
Automate the generation of geometry restraint information for refinement of novel ligands and improved geometry restraint information for standard ligands. A protein crystal can contain more than just protein and other simple molecules that most refinement programs can interpret. An unusual molecule can be included in the refinement via eLBOW from a number of chemical inputs. The geometry can be optimised using various levels of chemical knowledge including a semi-empirical quantum mechanical method known as AM1.
Input formats include
Output formats include
phenix.elbow [options] input_file.ext
or in a Python script
from elbow.command_line import builder
molecule = builder.run("input_file.ext", **kwds)
where the options are passed as a dictionary. The return object can be interrogated for information via the class methods. Output files from both techniques include a PDB file of the final geometry and a CIF file that contains the geometry restraint information for refinement. Other files are output as appropriate, such as edits and CIF files for linking the ligand to the protein. A final file contains the serialised data of the molecule in the Python pickle format.
To run eLBOW on a PDB file (containing one molecule)
phenix.elbow input_file.pdb
To run eLBOW on a PDB file containing protein and ligands. This will only process the ligands that are unknown to phenix.refine.
phenix.elbow input_file.pdb --do-all
To run eLBOW on a PDB file specifying a residue
phenix.elbow input_file.pdb --residue LIG
To use the atom names from a PDB file
phenix.elbow --smiles O --template input_file.pdb
To run eLBOW on a SMILES string
phenix.elbow --smiles="CCO"
or
phenix.elbow --smiles=input_file.smi
eLBOW performs a simple force-field geometry optimisation by default, however an AM1 geometry optimisation can be performed as follows.
phenix.elbow input_file.pdb --opt
To start from a specific geometry for the optimisation
phenix.elbow --initial_geometry input_file.pdb --opt
To use a separately installed GAMESS and do a HF/3-21G geometry optimisation
phenix.elbow input_file.pdb --gamess --basis="3-21G"
To not optimise, but use the input geometry as the final geometry
phenix.elbow --final_geometry input_file.pdb
eLBOW automatically adds hydrogens to the input molecules if there are less than a quarter of the possible hydrogens. This can be controlled using
phenix.elbow input_file.pdb --add-hydrogens=True
A common requirement is to add hydrogens to a ligand but retain the geometry and position relative to a protein. To do so use
phenix.elbow --final-geometry=input_file.pdb
To choice the base name of the output files
phenix.elbow input_file.pdb --output="output"
To change the three letter ID
phenix.elbow input_file.pdb --id=NEW
To change other attributes
phenix.elbow input_file.pdb --pdb-assign "resSeq=3 b=100"
Some of the attributes.
To output MOL2 format
phenix.elbow input_file.pdb --tripos
To output PDB Ligand output
phenix.elbow input_file.pdb --pdb-ligand
The options for chirality are "retain" (default), "both" and "enumerate". The default uses the chiral centres specified in the molecule input file or string as the guide for specifying the chirality in the restraints. The "both" will set all chiral centres in the input to "both". This means that each chiral centre can be either one or the other.
The "enumerate" option will write a restraints (CIF) and geometry (PDB) file for each permutation of the chiral centres. The number of permutation is 2**n (n = number of chiral centres). The files are labeled using the R/S notation. Each file has a string listing the configuration of the chiral centres based on the input order, e.g. _RSR, _RSS. The unappended file is the input configuration.
Cis/Trans moieties can occur centre on double bonds. SMILES can specify the exact configuration. Otherwise, eLBOW choices the lowest energy configuration. The "retain" choice does exactly that.
The "enumerate" option will write a restraints (CIF) and geometry (PDB) file for each permutation of the cis/trans moeity. The number of permutation is 2**n (n = number of cis/trans moieties). The files are labeled using the E/Z notation. Each file has a string listing the configuration of the cis/trans moiety based on the input order, e.g. _EEZ, _ZEE. The unappended file is the input configuration.
The pucker options are similar to the Chiral and Cis/Trans options. However, because it is a more complicated situation, the inputs are also complicated. Simiarly, the default is to use input and if not specified, the position of the groups on the ring are placed relative to the other groups on the ring atom randomly and in the axial (A) or equatorial (Q) position based on the simple force field optimisation.
The "enumerate" option will write a restraints (CIF) and geometry (PDB) file for each permutation of the pucker group moeity. The number of permutation is 2**n (n = number of pucker group moieties). The files are labeled using the A/Q notation invented by the author. Each file has a string listing the configuration of the pucker group moiety based on the input order, e.g. _AAA, _QAA. The unappended file is the input configuration.
The definition of the A and Q needs more clarification. Consider a ring in the chair configuration. At any atom in the ring, a group can be attached in the axial or equatorial position. Whether it is an "up equatorial" or "down equatorial" depends on the ring pucker and orietation.
To force a ring into a specific pucker, use REEL. The define what configuration of the pucker group use the "user_defined" option.
Moriarty NW, Grosse-Kunstleve RW, Adams PD: electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. *Acta Cryst.* 2009, **D65**:1074-1080.
| Option | Default & choices | Description of inputs and uses |
| --version | None | show program's version number and exit |
| --help | None | show this help message and exit |
| --long-help | None | show even more help and exit |
| --smiles | "" | use the passed SMILES |
| --file | "" | use file for chemical input |
| --msd | False | get SMILES using MSDChem code |
| --key | "" | use SMILES from smilesDB for chemical input |
| --keys | False | display smiles DB |
| --chemical-component | None | build ligand from chemical components (PDB) |
| --pipe | False | read input from standard in |
| --residue | "" | use only this residue from the PDB file |
| --chain | "" | use only this chain from the PDB file |
| --all-residues | None | retain all residues in a PDB file |
| --name | "" | name of ligand to be used in various output files |
| --sequence | "" | use sequence (limited to 20 residues and no semi-empirical optimisation) |
| --read-only | None | read the input but don't do any processing |
| --opt | False | use the best optimisation method available (currently AM1) |
| --template | "" | use file for naming of atoms e.g. PDB file |
| --mopac | False | use MOPAC for quantum chemistry calculations (requires MOPAC be installed) |
| --gamess | False | use GAMESS for quantum chemistry calculations (requires GAMESS be installed) |
| --qchem | False | use QChem for quantum chemistry calculations (requires QChem be installed) |
| --gaussian | False | use Gaussian for quantum chemistry calculations (requires Gaussian be installed) |
| --final-geometry | None | use this file to obtain final geometry |
| --initial-geometry | None | use this file to obtain the intital geometry for QM |
| --energy-validation | None | calculate the difference between starting and final energies |
| --restart | False | restart the optimisation with lowest previous geometry |
| --opt-steps | 60, "positive integer" | optimisation steps (currently for ELBOW opt only) |
| --opt-tol | default, loose, tight | optimisation tolerance = loose, default or tight |
| --chiral | retain | treatment of chiral centres = retain (default), both, enumerate |
| --ignore-chiral | None | ignore the chirality in the SMILES string |
| --skip-cif-molecule | None | ignore ligands in supplied CIF file(s) |
| --memory | 1Gb, "positive integer", "n Gb", "n Mb" | maximum memory mostly for quantum method |
| --method | "AM1" | run QM optimisation with this method, if possible |
| --basis | "AM1" | run QM with this basis, if possible |
| --aux-basis | None | run QM with this auxiliary basis, if possible |
| --random-seed | None | random number seed |
| --quiet | False | less print out |
| --silent | False | almost complete silence |
| --view | False | viewing software command |
| --reel | False | fire up restraints editor |
| --pymol | False | use PyMOL from the PHENIX install to view geometries |
| --overwrite | False | clobber any existing output files |
| --bonding | False | file that specifies the bond of the input molecule |
| --id | "LIG" | three letter code used in the CIF output |
| --xyz | False | output is also written in XYZ format |
| --tripos | False | output is also written in TRIPOS format |
| --sdf | False | output is also written in SDF format |
| --pdb-ligand | None | output is also written in PDB ligand format |
| --output | "algorithm determination" | name for output files |
| --pickle | False | use a pickle file to reload the topological information |
| --do-all | None | process all molecules in a PDB, TRIPOS or SDF file |
| --clean | False | DELETES "unnecessary" output files (dangerous) |
| --pdb-assign | "" | set the atom attributes in the PDB file |
| --heme | None | attempt to match HEME groups (experimental) |
| --add-hydrogens | "algorithm determination", True, False | override the automatic hydrogen addition |
| Option | Default & choices | Description of inputs and uses |
| --newton-raphson | None | use Newton-Raphson optimisation |
| --gdiis | False | use GDIIS optimisation |
| --quicca | False | use QUICCA optimisation |
| --user-opt | None | use user defined for quantum chemistry calculations |
| --user-opt-input-filena me | "" | input filename |
| --user-opt-xyz2input | "" | converts xyz file to QM program input |
| --user-opt-xyz-filename | "" | xyz filename |
| --user-opt-script-filen ame | "" | run script filename |
| --user-opt-program | "" | QM optimisation program run script or program invocation command |
| --user-opt-output-filen ame | "" | output filename |
| --user-opt-output2xyz | "" | converts QM program output to xyz file |
| --write-hydrogens | True, False | override the automatic writing of hydrogens to PDB and CIF files |
| --auto-bond-cutoff | 2.0, "float between 0.5 and 3" | set the max bondlength for auto bond detection |
| --write-redundant-dihed rals | None | control the writing of redundant dihedrals |