Subsections

6.5 Using MASC

This section has examples of using the MASC (see section 4.3.12) variants of the scoring functions available in FRED. MASC requires that ligands be specially prepared by docking them to a set of reference sites and storing the resulting scores with the ligands. This will be done automatically by FRED if it detects that the input ligands do not have the required MASC data using a standard set of reference sites built into FRED. Calculating the MASC data is computationally expensive since each ligand must be docked to the reference sites (of which there are 12 in FRED's standard set) before docking to the target receptor. However this calculation can be done once for a given set of ligands, and the same data re-used when those ligands are docked to any number of different targets (in which case the computational cost for using MASC is negligible after the initial calculation).

6.5.1 Scoring with MASC

6.5.1.1 Using a single MASC scoring function

fred -dbase my_ligands.oeb.gz \
     -rec my_receptor.oeb.gz \
     -chemgauss3_masc

6.5.1.2 Description

Docks my_ligands.oeb.gz to my_receptor.oeb.gz and outputs the 1000 molecules as scored by the MASC variant of the Chemgauss3 scoring function.

The contents of emphmy_ligands.oeb.gz affect how the run proceeds as follows:

my_ligands.oeb.gz contains :

a standard set of multiconformer molecules: FRED will automatically generate the needed MASC data by docking the ligands to 12 internal reference sites before docking the ligands to my_receptor. The run time of the job will be approximately 13-fold longer than a standard FRED run because FRED must dock each ligand 13 times (12 reference sites + the target protein). FRED will also output a copy of the my_ligands.oeb.gz file to masc_ligands.oeb.gz with all the calculated MASC data tagged to it. The masc_ligands.oeb.gz file can then be used in future runs against this or other targets when the MASC variant of Chemgauss3 is used (it may also be used when doing standard non-MASC scoring).
multiconformer molecules with the Chemgauss3 MASC data: FRED will use the existing MASC data, and will not need to dock the molecules to the reference sites. Run time will be the same as a normal run using Chemgauss3.

6.5.1.3 Parameters

-dbase

my_ligands.oeb.gz

This tells FRED where the ligands it is going to dock are, in this case the file my_ligands.oeb.gz. The ligand file should have multiple conformers of all flexible ligands. It also may or may not contain MASC data. The run will proceed differently depending on whether MASC data is present or not, see the description above.

-rec

my_receptor.oeb.gz

This specifies a receptor file to dock the ligand to. The receptor file must be created prior to running FRED with this command line. This file can be created by FRED or by the fred_receptor GUI.

-chemgauss3_masc

Tells FRED to score ligands with the MASC variant of Chemgauss3.

6.5.1.4 Output

setup.txt: A file with the settings of all of FRED's parameters. Note that there will be many more parameters in this file than those specified on the command line because many parameters have default values. This file will be written at the beginning of the run.
receptor.oeb.gz: This file contains a copy of the receptor site used for the run. This file will be written at the beginning of the run.
status.txt: This file will be written every few seconds by FRED and indicates the status of the run.
masc_chemgauss3_docked.oeb.gz: contains the structure o the top 1000 docked ligands as ranked by the MASC variant of Chemgauss3.
masc_chemgauss3_scores.txt: list the names, scores and SMILES representation of the top 1000 docked ligands as ranked by the MASC variant of Chemgauss3 in a text format.

Additionally if my_ligands.oeb.gz did not contain the required MASC data the following file will be outputted.

masc_ligands.oeb.gz: A copy of the my_ligands.oeb.gz file that also hold the MASC data FRED calculated. The masc_ligands.oeb.gz contains all the conformers and data of the original my_ligands.oeb.gz file and can be used in place of the original file in any program.

6.5.2 Using multiple MASC and other scoring functions

6.5.2.1 Command Line

fred -dbase my_ligands.oeb.gz \
     -rec my_receptor.oeb.gz \
     -plp_masc \
     -plp \
     -chemgauss3_MASC \
     -oechemscore

6.5.2.2 Description

my_ligands.oeb.gz will be docked to my_receptor.oeb.gz. Docked ligands will be scored and outputted to hitlists using PLP, the MASC variant of PLP, the MASC variant of Chemgauss3 and OEChemscore. Also two consensus hitlists will be maintained, one which uses the MASC variant scoring functions and one which uses the standard non-MASC scoring functions. If there were only one MASC or non-MASC scoring function selected, that type of consensus hitlist would be be maintained.

The contents of my_ligands.oeb.gz affect how the run proceeds as follows:

my_ligands.oeb.gz contains :

a standard set of multiconformer molecules: FRED will automatically generate the needed MASC data by docking the ligands to 12 internal reference sites before docking the ligands to my_receptor. The run time of the job will be approximately 13-fold longer than a standard FRED run because FRED must dock each ligand 13 times (12 reference sites + the target). FRED will also output a copy of the my_ligands.oeb.gz file to masc_ligands.oeb.gz with all the calculated MASC data tagged to it. The masc_ligands.oeb.gz file can then be used in future runs against this or other targets when the MASC variant of Chemgauss3 or PLP are used (you can also use it when doing standard non-masc scoring).
multiconformer molecules with either PLP or Chemgauss3: Run will proceed as if the input molecules did not have any MASC data (i.e. docking to the reference sites will be required, and the run time will be long).
multiconformer molecules with PLP and Chemgauss3 MASC data: FRED will use the existing MASC data, and will not need to dock the molecules to the reference sites. Run time will be the same as a normal run.

6.5.2.3 Parameters

-dbase

my_ligands.oeb.gz

This tells FRED where the ligands it is going to dock are, in this case the file my_ligands.oeb.gz. The ligand file should have multiple conformers of all flexible ligands. It also may or may not contain MASC data. The run will proceed different depending on if MASC data is present, see the description above.

-rec

my_receptor.oeb.gz

This specifies a receptor file to dock to the ligand too. The receptor file must be created prior to running FRED with this command line. This file can be created by FRED or by the fred_receptor GUI.

-plp

Tells FRED to score ligands with PLP.

-plp_masc

Tells FRED to score ligands with the MASC variant of PLP.

-chemgauss3_masc

Tells FRED to score ligands with the MASC variant of Chemgauss3.

-oechemscore

Tells FRED to score the ligands with OEChemscore.

6.5.2.4 Output

setup.txt: A file with the settings of all of FRED's parameters. Note that there will be many more parameters in this file than those specified on the command line because many parameters have default values. This file will be written at the beginning of the run.
receptor.oeb.gz: This file contains a copy of the receptor site used for the run. This file will be written at the beginning of the run.
status.txt: This file will be written every few seconds by FRED and indicates the status of the run.
plp_docked.oeb.gz: contains the structure of the top 1000 docked ligands as ranked by PLP.
plp_scores.txt: list the names, scores and SMILES representation of the top 1000 docked ligands as ranked by PLP in a text format.
masc_plp_docked.oeb.gz: contains the structure of the top 1000 docked ligands as ranked by the MASC variant of PLP.
masc_plp_scores.txt: list the names, scores and SMILES representation of the top 1000 docked ligands as ranked by the MASC variant of PLP in a text format.
masc_chemgauss3_docked.oeb.gz: contains the structure of the top 1000 docked ligands as ranked by the MASC variant of Chemgauss3.
masc_chemgauss3_scores.txt: list the names, scores and SMILES representation of the top 1000 docked ligands as ranked by the MASC variant of Chemgauss3 in a text format.
oechemscore_docked.oeb.gz: contains the structure of the top 1000 docked ligands as ranked by OEChemscore.
oechemscore_scores.txt: list the names, scores and SMILES representation of the top 1000 docked ligands as ranked by OEChemscore in a text format.
masc_consensus_docked.oeb.gz: contains the structure of the top 100 docked ligands and ranked by consensus of MASC PLP and MASC Chemgauss3.
masc_consensus_scores.txt: lists the names, scores and SMILES representation of the top 1000 docked ligands as ranked by MASC PLP and MASC Chemgauss3. The file is in a text format.
consensus_docked.oeb.gz: constains the structure of the top 100 docked ligands and ranked by consensus of PLP and OEChemscore.
consensus_scores.txt: lists the names, scores and SMILES representation of the top 1000 docked ligands as ranked by PLP and OEChemscore. The file is in a text format.

Additionally if my_ligands.oeb.gz did not contain the required MASC data the following file will be outputted.

masc_ligands.oeb.gz: A copy of the my_ligands.oeb.gz file that holds the MASC data FRED calculated. The masc_ligands.oeb.gz contains all the conformers and data of the original my_ligands.oeb.gz file and can be used in place of the original file.

6.5.3 Preparing ligands

6.5.3.1 Command Line

fred -dbase my_ligands.oeb.gz \
     -shapegauss_MASC \
     -plp_MASC \
     -chemgauss2_MASC \
     -chemgauss3_MASC \
     -chemscore_MASC \
     -oechemscore_MASC \
     -screenscore_MASC

6.5.3.2 Description

This command tells FRED to calculate Shapegauss, PLP, Chemgauss2, Chemgauss3, Chemscore, OEChemscore and Screenscore MASC data for all the ligands in my_ligands.oeb.gz, by docking them to 12 internal reference sites (hence the total time for this process will be about 12 times that of a normal docking run).

A copy of my_ligands.oeb.gz will be outputted to masc_ligands.oeb.gz which contains all the original information of my_ligands.oeb.gz (i.e. masc_ligands.oeb.gz can be used anywhere my_ligands.oeb.gz could be) plus MASC data for the scoring functions. The masc_ligands.oeb.gz can then be used in future FRED runs against any target and the use of MASC will not slow those runs down (for the scoring functions the data is calculated for).

6.5.3.3 Parameters

-dbase

my_ligands.oeb.gz

-shapegauss_masc

tells FRED to calculate Shapegauss MASC data.

-plp_masc

tells FRED to calculate PLP MASC data.

-chemgauss2_masc

tells FRED to calculate Chemgauss2 MASC data.

-chemgauss3_masc

tells FRED to calculate Chemgauss3 MASC data.

-chemscore_masc

tells FRED to calculate Chemscore MASC data.

-oechemscore_masc

tells FRED to calculate OEChemscore MASC data.

-screenscore_masc

tells FRED to calculate Screenscore MASC data.

6.5.3.4 Output

setup.txt: A file with the settings of all of FRED's parameters. Note that there will be many more parameters in this file than those specified on the command line because many parameters have default values. This file will be written at the beginning of the run.
status.txt: This file will be written every few seconds by FRED and indicates the status of the run.
masc_ligands.oeb.gz: A copy of the my_ligands.oeb.gz file that also hold the MASC data FRED calculated. The masc_ligands.oeb.gz contains all the conformers and data of the original my_ligands.oeb.gz file and can be used in place of the original file in any program.

6.5.4 Preparing ligands with your own reference sites

6.5.5 Preparing ligands

6.5.5.1 Command Line

fred -dbase my_ligands.oeb.gz \
     -reference_receptors my\_reference\_receptors.txt
     -shapegauss_MASC \
     -plp_MASC \
     -chemgauss2_MASC \
     -chemgauss3_MASC \
     -chemscore_MASC \
     -oechemscore_MASC \
     -screenscore_MASC

6.5.5.2 Description

This command tells FRED to calculate Shapegauss, PLP, Chemgauss2, Chemgauss3, Chemscore, OEChemscore and Screenscore MASC data for all the ligands in my_ligands.oeb.gz, by docking them to the reference sites listed in the text file my_reference_receptors.txt.

Note that the run time for this calculation is fairly invariant if 1 or all of the scoring functions are used, so in general there is no reason not to prepare your ligands with as much MASC data as possible. One exception is Zapbind the calculations for which are lengthy therefore calculating Zapbind MASC data will increase the runtime significantly. Note that if you want to calculated MASC data for the ligand based scoring functions (i.e. CGO and CGT), you reference receptors must all contain bound ligands.

6.5.5.3 Parameters

-dbase

my_ligands.oeb.gz

-reference_receptors

my_reference_receptors

Tells FRED to use the receptors listed in my_reference_receptors.txt to calculate the MASC data. The format of my_reference_receptors.txt is a text file with the name of one receptor file per line. The minimum number of receptor files is 3, 6-10 is recommended.

Example reference file

my_reference_rec1.oeb.gz
my_reference_rec2.oeb.gz
my_reference_rec3.oeb.gz
my_reference_rec4.oeb.gz
my_reference_rec5.oeb.gz
my_reference_rec6.oeb.gz
my_reference_rec7.oeb.gz
my_reference_rec8.oeb
my_reference_rec9.oeb

-shapegauss_masc

tells FRED to calculate Shapegauss MASC data.

-plp_masc

tells FRED to calculate PLP MASC data.

-chemgauss2_masc

tells FRED to calculate Chemgauss2 MASC data.

-chemgauss3_masc

tells FRED to calculate Chemgauss3 MASC data.

-chemscore_masc

tells FRED to calculate Chemscore MASC data.

-oechemscore_masc

tells FRED to calculate OEChemscore MASC data.

-screenscore_masc

tells FRED to calculate Screenscore MASC data.

6.5.5.4 Output

setup.txt: A file with the settings of all of FRED's parameters. Note that there will be many more parameters in this file than those specified on the command line because many parameters have default values. This file will be written at the beginning of the run.
status.txt: This file will be written every few seconds by FRED and indicates the status of the run.
masc_ligands.oeb.gz: A copy of the my_ligands.oeb.gz file that also hold the MASC data FRED calculated. The masc_ligands.oeb.gz contains all the conformers and data of the original my_ligands.oeb.gz file and can be used in place of the original file in any program.

				FRED Fast Rigid Exhaustive Docking

				FRED Fast Rigid Exhaustive Docking