- -prot <filename>¶
Optional protein used to mask density. This model is used to mask away density where the ligand should not be placed. While the protein is not required, it is highly recommended.
File type Extension OEBinary .oeb .oeb.gz SDF .sdf .mol .sdf.gz .mol.gz MOL2 .mol2 .mol2.gz PDB .pdb .ent .pdb.gz .ent.gz MacroModel .mmod .mmod.gz
Fragments are fit taking the input fragment cocktail and, one at a time, fitting each fragment against each region of detected density. Once a fragment has been placed, it is further analyzed to ensure that all possible orientations of the fragment have been sampled. In poor density, several orientations may fit equally well. To break ties, FLYNN scores each pose with the following scores:
o RSCC (real space correlation coefficient) This is a measure of fit to electron density. [AFITT-CL Jones-1991]_
o PLP Piecewise-linear potential. [AFITT-CL Verkhivker-2000]_
o Chemscore [AFITT-CL Eldridge-1997]_
The docking scores are not used to fit the molecule, they are only used to rank the output. Unless highly symmetric molecules are being input, the real space correlation coefficient (RSCC) is the preferred method of ranking results to density.
All scores are annotated to the output ligands using SD data when appropriate (.SD and .OEB output) or using the PDB remark field:
Example PDB output REMARK OpenEye Flynn MMFF/Shape v 2.1.0 REMARK Stereo Variant: 1 REMARK Blob: 1 REMARK Conformer: 1 REMARK Tanimoto Shape: 0.2004 REMARK Tanimoto MMFF/Shape: 0.2034 REMARK Local Strain: 4.9316 REMARK RSCC: 0.529438 REMARK PLP: -51.395416 REMARK Chemscore: -16.288113
Example SDF output > <Tanimoto MMFF/SHAPE> 0.2034 > <Tanimoto Shape> 0.2004 > <Overlap> 364.767659122018 > <Fit Overlap> 781.301114117834 > <Local Strain> 4.9316 > <Lambda> 1.600000023842 > <Ref Overlap> 1371.829467773438 > <Stereo> 1 > <Blob> 1 > <Conformer> 1 > <RSCC> 0.529438 > <PLP> -51.395416 > <Chemscore> -16.288113
To use fragment mode, please add the “-fragment” option to the command line. In future versions of FLYNN, this will most likely become the default setting.
The output of the fragment fitting process is a file for each density region that includes the fragments fit to the region sorted from best-fit to worst fit. For example:
> flynn -in fragments.smi -out 2IKO_cocktail.sdf ...
would result in the files:
2IKO_cocktail_blob001.sdf 2IKO_cocktail_blob002.sdf 2IKO_cocktail_blob003.sdf
one for each blob found. The first molecule in the file is the best fit to the density.
To sort using another measure, for instance, PLP, use the sort flag:
> flynn -sortBy plp -in fragments.smi -out 2IKO_cocktail.sdf ...
When oeb format is used, the blob is also stored in the OEB file. When using VIDA, simply expand the molecule to investigate the blobs density.
- -param <parameter filename>¶
A parameter file is a text file that lists parameter settings to be used during a run. If a parameter is specified both on the command line and in the parameter file, the value specified on the command line is used.
The format of the parameter file is as follows:
- One parameter per line
- For non-list parameters one key-value pair per line.
- For list parameters a key followed by all the values.
- Boolean parameters must be listed as a key followed by true or false.
- The parameter file may not contain the -param parameter.
- Lines beginning with # are considered comments
- -prefix <file prefix>¶
Define the default prefix to use for loggging and report file generation.
This -prefix is overridden when using the -reporthtml or -reportfile command line options.
- -manualSearch <filename>¶
Use the input molecule to generate a box volume. All density inside this box will be used to place the ligand.
- -boxpad <number>¶
Pad the box created with the -manualSearch flag by an amount in Ångströms.
Automatically search for blobs first, if now suitable blobs are found, use the supplied box to bound density.
Use the supplied density as it is; do not try to find suitable blobs inside the density. Note that the supplied density has to be pretty close to the actual ligand density for this to work
- -distance <value>¶
Reject blobs whose average distance to the protein is greater than this value.
Do not generate conformations for the ligand; use only the supplied conformations.
- Use the MMFF94s variant of the MMFF94 forcefield ( this uses planar aniline nitrogens ).
- -reportfile <filename>¶
- File location for writing the report file. This is a comma separated file containing specifics about the results.
Smiles,Blob,Stereo Variant,Conformer,Tanimoto Shape,Tanimoto MMFF/SHAPE,Local Strain CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C,1,,,0.4110,0.4296,1.342 CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C,1,,,0.313,0.3704,4.553 CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C,1,,,0.3265,0.3628,5.223
- -resname <name>¶
Set the output residue name to <name>. <name> must be less than or equal to three characters in length. This forces the output residue to be named <name> even if the residues structure does not match a known deposited residue.
- -chainid <chainid>¶
Forces the ligand to be placed in the chain <chainid>
- -sortAllChiral <true/false>¶
If set to true, when multiple chiralities are enumerated, sort all chiralities from best to worst per blob, otherwise sort chiral structures independently. For example, if two blobs are found, then the output will have all chiral structures sorted from best fit to worst fit for the first blob, and then all chiral structures sorted from best fit to worst fit for the second blobs, etc Note that the second blob may contain better fits than the first. (Note: This may interleave chiral structures).
- This is a boolean flag that controls the level of
detail written to the log file. By default FLYNN will only write minimal information to the console. Verbose logging will cause more information to be written to the log file in order to follow behavior during program execution.
MTZ File Options¶
Automatically try to open the mtz file using the DELWT and FDELWT columns from REFMAC5 mtz files.
- -Fc <columnname>¶
Column to use for Fc. Note, to load arbitrary columns, you can use the *-Fc** and -Phic columns and the Fc maptype.*
- -Fdelwt <columnname>¶
Column to use for Fdelwt or difference map amplitudes
- -Fobs <columnname>¶
Column to use for FObs.
- -Fwt <columnname>¶
Column to use for Fwt or regular map amplitudes.
- -Phic <columnname>¶
Column to use for Phic.
- -Phidelwt <columnname>¶
Column to use for Phdelwt or difference map phases.
- -Phiwt <columnname>¶
Column to use for Phwt or regular map phases.
- The map type to use for fitting. Fo-Fc, Fc, 2Fo-Fc, 3Fo-Fc, Fwt,
Specify the format of the refinement dictionary. Legal values for refinement dictionaries are ‘refmac’, ‘phenix’ and ‘buster’. Refinement dictionaries are always written out using the designation specified in the ‘-split’ command. For best results, use -split when writing out cif files when using FLYNN.
Force enumeration of all stereochemical centers. Otherwise, only missing stereo chemistry will be enumerated.
Set the number of initial rigidly fit overlays to optimize into density.
Perform only a preliminary check of the data to see if fitting is possible. (This flag is meaningless without the -reporthtml flag).
Generate an html report of the fitting process. This is a useful first step to verify the data. It also includes a 2D image of the ligand that is being fit in order to verify bond orders. All output of FLYNN will be captured in the specified html file.
Comma separated list of residues to use as distance constraints. If residues are specified, the -distance flag will use the residues to reject blobs that are too far away. Note that with a residue list, the distance computed is a minimum distance, not an average distance. Residues must be specified as <residue number><chain id>. For example: 120C,134C. On Windows, double quotes must be added to specify two or more residues, i.e. -residues “120C,134C”.
If the input ligand has 3D coordinates, this calculates the RMS distance to the ligand and records it in the molecule. If -split is on, it also records it in the file name.
Split the result into different files. Each filename is annotated with the resulting shape score so that when the output directory is listed alphabetically, the best scores will be displayed in order. In the case where the output format is pdb the ligand fitting results are written in REMARK statements at the top of the file.
The splits are labeled as follows outputname_n###_b###_s###_c### where n### is the number of the ordered results, b### is the blob for the result, s### is the stereovariant and c### is the number of the conformer fit as ordered by MMFF/Shape.
By default FLYNN outputs hydrogens of the resulting poses. Setting this to true will not output hydrogens. It is always recommended to output hydrogrens for ligands in order to keep their chemistry the same as flynn’s internal optimizer. Only suppress hydrogens if your refinement package doesn’t handle hydrogen names correctly.
Force serial numbers to be unique when writing out the resulting pdb file for use in the refinement package. This is usually caused by adding hydrogens to the ligand outside of the context of the protein and then using it in conjunction with the original PDB structure.
Fragment Fitting Options¶
Density is searched for each input ligand. This flag sets the minimum tanimoto overlap for which to consider two blobs the same. When pruning similar blobs, the larger is taken.
[default = 0.45]
Choose the fragment sorting function, tanimoto, rscc (real space correlation coefficient), plp (piecewise linear potential) or chemscore.
The fragments are fit in the normal fashion (tanimoto), but then re-scored and sorted using the chosen metric.
[default = rscc]
3D Construction Options¶
These are advanced conformer generation parameters. Normally, they do not need to be adjusted. Please consult the OMEGA manual for assistance:
Controls the MMFF energy window when generating initial conformations. Normally, this setting does not need to be adjusted, however in some cases large floppy molcules may require an adjustment. This setting is in kcals/mol.
[default = 15.0]