Cscore Manual

CScore™ Manual
SYBYL®-X 2.1
Mid 2013
1699 South Hanley Rd. Phone: +1.314.647.1099

St. Louis, MO Fax: +1.314.647.9241
63144-2917 http://www.certara.com
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Selected software programs for methodologies contained or documented herein are covered by one or more of the
following patents: AllChem: US 7,860,657; Comparative Molecular Field Analysis (CoMFA): US 5,025,388; US
5,307,287; US 5,751,605; AT E150883; BE 0592421; CH 0592421; DE 691 25 300 T2; FR 0592421; GB 0592421;
IT 0592421; NL 0592421; SE 0592421. HQSAR: US 6,208,942. Embedded NLM: US 6,675,103. Topomers: US
6,185,506; US 6,240,374; US 7,184,893; US 7,212,951. TopCoMFA: US 7,329,222. DBTop: US 7,330,793. OptiSim:
US 6,535,819. Surflex software programs for chemical analysis by morphological similarity: US 6,470,305 B1.
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CScore Table of Contents
1. Introduction to CScore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.1 What is New with CScore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.2 License Requirements for CScore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2. CScore Tutorials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.1 CScore and Surflex-Dock in SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2.2 Using CScore with Externally-Generated Results . . . . . . . . . . . . . . . . . . . . . 11
3. Run CScore via the Menubar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

3.1 Run CScore while Docking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.2 Use CScore in a Spreadsheet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.3 CScore Subset Extraction Tool . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
4. Run CScore via the Command Line . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

4.1 SYBYL Command: CSCORE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
4.2 CScore Standalone Utility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
5. CScore Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
5.1 Purpose of CScore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5.2 CScore Input Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
5.3 Generating a Consensus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
5.4 G_Score . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
5.5 PMF_Score . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.6 D_Score . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
5.7 ChemScore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
5.8 Total_Score . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
5.9 CScore Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
6. CScore Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
6.1 CScore Parameters: $TA_MOLTABLES/cscore.par . . . . . . . . . . . . . . . . . . 46
SYBYL-X 2.1 CScore 3

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1. Introduction to CScore
CScore (Consensus Score) integrates a number of popular scoring functions for

ranking the affinity of ligands bound to the active site of a receptor. The
strengths of individual scoring functions combine to produce a consensus that is
more robust and accurate than any single function for evaluating ligand-receptor
interactions.
CScore can be run in a number of ways:

• Docking Graphical Interface
Both the single- and multiple-molecule dialogs allow you to run CScore
on the results, and now contain a CScore Details button. Press this
button to access the CScore Details dialog.
• Molecular Data Explorer Menubar
The CScore menu item appears in a docking spreadsheet (one in which
the “ORIGIN” attribute is set to “DOCKING”). You can specify the
name of the protein file, add the CScore scores to the spreadsheet, and
generate a consensus from a selected set of columns (and rows).
• SYBYL Command: CSCORE
Use the command CSCORE with SYBYL to create a new column with the
“consensus score” of a selected group of numerical columns.
• System Utility: CScore
Outside of SYBYL use the command $TA_BIN/CScore to evaluate
protein/ligand complexes with various scoring functions. Ligand and/or
protein sidechain relaxation can be included.

What is New with CScore
1.1 What is New with CScore

Dramatic Speed Improvements
Improvements have been made to enhance the speed of CScore, particularly
with large runs.The number of structures processed per CPU per hour has gone
from approximately 260 structures in SYBYL-X 2.0 to approximately 157,000
structures in SYBYL-X 2.1.
The time for loading results has also dropped significantly. Loading results for
5,000 ligands (20 poses per ligand) took days with SYBYL-X 2.0, it now takes
approximately 6 minutes with SYBYL-X 2.1.
Part of the speed-up in loading results is due to use of CScore’s CSV single file
output format. A user wishing to fix an old run that was opened in the result
browser but did not have CScore data imported into the final dataset (despite
being calcultaed) can simply remove all SLN files from the job directory, and
then reopen the job in the results browser. This triggers the recreation of the
SLN file along with all associated data import.
Status updates are now displayed and there is a status bar to confirm that the
process is continuing.
CScore Subset Extractor

Progress reporting is now provided in CScore subset extractor jobs.
The extraction process has been streamlined to single pass mol2 file processing,
rather than performing one scan per molecule.
A parsing issue involving Multi-Mol2 files has been resolved in the CScore
subset extractor.
MDBs are no longer supported as input or output options for CScore. As a

result, the MDB option and the associated Output Options section in the
CScore Output Details dialog have been removed.
Docking Properties in Results Spreadsheet

Some of the docking properties were absent from CScore consensus calcula-
tions in the results spreadsheet. This issue has been resolved.
SYBYL-X 2.1 will not extract CScores from jobs created in SYBYL-X 2.0 or
earlier.
6 CScore SYBYL-X 2.1

License Requirements for CScore
1.2 License Requirements for CScore

SYBYL-X Suite Licensing
SYBYL-X introduced a simplified licensing scheme in which the “SYBYL”
license provides access to CScore in unlimited amount.
See also the Docking Suite Manual for additional license requirements.
Module-Based Licensing
SYBYL continues to run with a license file issued before the SYBYL-X release.
In that context:
• CScore computation requires a “CScore” license.
• For fast CScore processing from the SYBYL interface to docking, you
will need as many “CScore” licenses as docking licenses.
• See Also: Docking Suite Manual for additional license requirements

2. CScore Tutorials
The exponential increase in the number of protein crystal structures available

from the Protein Data Bank has led to a renewed interest in the direct approach
to drug design—that is, directly docking a potential ligand into the active site of
a receptor.
• CScore and Surflex-Dock in SYBYL on page 10
• Using CScore with Externally-Generated Results on page 11

2. CScore Tutorials
CScore and Surflex-Dock in SYBYL
2.1 CScore and Surflex-Dock in SYBYL

Surflex-Dock uses an empirical scoring function and a patented search engine to
dock ligands into a protein's binding site. Docking is guided by the protomol, an
idealized representation of a ligand that makes every potential interaction with
the binding site.
The Surflex-Dock graphical user interface (described in the Docking Suite

Manual) provides an easy access to CScore. You may want to include CScore
when running the Surflex-Dock tutorial.

2. CScore Tutorials
Using CScore with Externally-Generated Results
2.2 Using CScore with Externally-Generated

Results
You will use a molecular spreadsheet containing the best docked results for 10
structures extracted from a database. For this tutorial, we calculated 2D finger-
prints from the NCI81K database. Diversity selection produced 8000
compounds. The first ten were selected, docked, and their best results saved in a
database.
Upon successful completion of this tutorial, you will know how to use CScore
to further investigate protein-ligand docking results.
A Matter of Time: This tutorial requires a couple of minutes of personal time.
2.2.1 Retrieve the Spreadsheet and Associated Receptor

1. It is always a good idea to clear the screen and reset the display before starting.
! > Delete Everything
! Click to reset all rotations and translations.
2. Open the spreadsheet containing the docking results.
! Click on the SYBYL toolbar.
! Set Files of Type to Spreadsheet.
! Select [$TA_DEMO] in the Bookmarks list then double-click

docked_ligands.tbl in the Selection list.
The spreadsheet is displayed. It contains the extracted ligand and the 10

compounds as well as their docking scores (as could be obtained from external
programs) in the column labeled Docking_Score.
3. Check the spreadsheet’s ORIGIN attribute.
For CScore to work, the table attribute ORIGIN must exist and be set to
DOCKING. This has already been done for this spreadsheet. You can check this
by typing a command.
! In the command console type: table attribute list origin
The console reports: DOCKING.
When you work with your own data, see Use CScore in a Spreadsheet on page
18 for procedural details.

2. CScore Tutorials
4. Identify the Mol2 file containing the associated protein, carboxypeptidase A.
! MDE: CScore > Set Receptor
! Select [$TA_DEMO] and docked_receptor.mol2 then press OK.
2.2.2 Run CScore
Run CScore With Rigid Ligands
5. This is a small spreadsheet, so you will run CScore on all rows. If you don’t
specify the rows of interest, all will be selected automatically.
! MDE: CScore > Run CScore
In the CScore dialog all the scoring functions are toggled on by default.
! Press OK in the CScore dialog to start the computation.
CScore proceeds and adds five score columns to the spreadsheet.
6. The consensus score was automatically computed from the five scores and
stored in the CSCORE column.
Consensus scores can range from 0 to 5, where 5 indicates that a ligand was
judged good by all functions. In the spreadsheet, several ligands were
considered good by groups of multiple functions. Structures with scores of 3, 4
or 5 merit further consideration. Structures with a consensus score of 0 are
consistently considered bad by all scoring functions and should be dropped.
Note: When working with your own data, you need to look more closely at
those structures which rate towards the top in some functions and towards the
bottom in others, since such structures might be examples where scoring
functions aren’t well parameterized or applicable.
Run CScore With Relaxed Ligands
7. Delete the 5 columns that were created by the CScore run. CScore will
recompute them, so leaving them in would clutter the spreadsheet.
! Delete the five columns created by the CScore run.
8. Run CScore again.

! MDE: CScore > Run CScore
! In the CScore dialog toggle on the option to Relax Molecules and

Score.

2. CScore Tutorials
! Press OK.
The Tripos force field will be used to minimize each ligand as it is docked in
the receptor.
CScore adds 10 columns to the spreadsheet. The first half are the same as those
created with rigid ligands. The others have the letter R in their name.
9. Compare the two CScore columns: CSCORE (unrelaxed) and CSCORER

(relaxed).
Relaxing the ligands increased some of the consensus scores. However, others
do not rate as well after relaxation.
2.2.3 Final Notes

This concludes the test of CScore for externally-generated results. We suggest
that you perform the same operations using a larger set of docked results from
your own research.
A consensus can be built from any number of columns containing numeric data.
If no rows are selected, all rows will be used.
10. Close the spreadsheet, but do not save it since it resides in SYBYL’s
$TA_DEMO directory.
! MDE: File > Close
! Press No at the prompt to save it to a table file.

3. Run CScore via the Menubar
• Run CScore while Docking on page 16
• CScore Details on page 16
• Use CScore in a Spreadsheet on page 18
• What is a Docking Spreadsheet? on page 18
• The CScore Menu in a Spreadsheet on page 18
• CScore Subset Extraction Tool on page 20
• Define the CScore Function on page 24
• Select the CScore Output Formats on page 25
Additional Information:
Tailor subject CSCORE for parameters affecting the computation of scoring
functions

Run CScore while Docking
3.1 Run CScore while Docking

The Docking dialog allows you to include a CScore calculation at the end
docking run.
Licensing: See License Requirements for CScore on page 7.
• Run CScore via the Command Line on page 27
• CScore Parameters on page 45
• Tailor subject CSCORE in the Tailor Manual.
Applications > Docking Suite > Dock Ligands
The Docking dialog is described in the Docking Suite Manual.
Perform CScore Check the box to compute additional scores and create
Calculation the corresponding columns in the spreadsheet. The con-
sensus score is then generated from the combination of
these scores and the Surflex-Dock score.
CScore Details Access the CScore Details dialog and select the addi-
tional scoring functions and specify whether structure
relaxation should occur.
See the CScore Theory on page 33 for a description of available scoring

functions.
3.1.1 CScore Details

To select the scoring functions to be used when running CScore. Note: Some of
the scoring functions (in particular G-score) used by CScore give qualitatively
different results depending on whether the structure has a kekule or an aromatic
representation.
Access:
Press the CScore Details button in the Docking dialog.

Run CScore while Docking
Parameters The default parameter file to use with the CScore pro-
gram itself ($TA_MOLTABLES/flexx_cscore.par).
Read about CScore Parameters on page 45.
Relax Structure Relax the protein/ligand pair, using the various options
in the associated parameter file.
Score Relaxed Generate additional CScore scores for the relaxed pro-
tein/ligand pair. This option is available only if the
Relax Structure box has been checked.
Scoring Func- Toggle on or off the various scoring functions (see
tions CScore Theory on page 33) to compute additional
scores and create the corresponding columns in the
spreadsheet. The consensus score is then generated
from the combination of these scores and the score
computed by the selected docking engine.
Some of the scoring functions (in particular G-score)
give qualitatively different results for Kékulé and aro-
matic representations.
CScore Direc- CScore files (.cso) are written to a subdirectory (by
tory default CScore) of the docking job directory unless a
file named CScoreOutputLocation (also in the job
directory) specifies a different location. If that file does
not exist, the .cso files are expected to be in the job
directory.

Use CScore in a Spreadsheet
3.2 Use CScore in a Spreadsheet

3.2.1 What is a Docking Spreadsheet?
The CScore menu is available only in a molecular spreadsheet identified as the
results of a docking calculation.
• Typically, such spreadsheets are created by Surflex-Dock.
• Alternatively, you may provide your own spreadsheet in which the rows
are docked ligands.
Spreadsheet of Surflex-Dock results:

The table attribute ORIGIN is already set to DOCKING,SURFLEXDOCK.
If the spreadsheet contains the results of another docking program:

! You must create the ORIGIN attribute and set it to DOCKING.
• Interactively, at the command line:
table attribute create ORIGIN string
table attribute set ORIGIN DOCKING
• In an SPL script:
if %not(%table_attribute(ORIGIN))
table attribute create ORIGIN string
endif
table attribute set ORIGIN DOCKING
! In order to have the CScore menu added to the spreadsheet’s

menubar you must save the spreadsheet to a table file (.tbl), close it,
then reopen it.
3.2.2 The CScore Menu in a Spreadsheet

When a docking spreadsheet is opened, the CScore menu is available on its
menubar.
Set Receptor
Prompts for the name of the Mol2 file containing the protein to which the
ligands were docked. The file must contain the protein with the correct atom
and bond types. All valences must be filled unless charged residues are present.

Use CScore in a Spreadsheet
Run CScore
Generates a column for each selected scoring function with a value for each
selected ligand. If no ligands are selected, all are used. If relaxation is
requested, a second set of columns with relaxed scores is generated.
CScore creates new columns with successive invocations.
Get Consensus
Generates a column with the consensus score, built from every selected column
and ligand. At least one column must be selected. If no ligands are selected, all
are used.

CScore Subset Extraction Tool
3.3 CScore Subset Extraction Tool

CScore can create a significant amount of data. This tool gives you more flexi-
bility in interrogating your data. Use it to generate subsets of docked ligands
based on various function and consensus scores (read about Generating a
Consensus on page 36).
Applications > Docking Suite > CScore Subset
Jobname Press [...] to access a file browser and identify the

directory containing the docking run.
The information box reports the number of answers
found for unrelaxed and (possibly) relaxed ligands, and
the scoring functions available for each set.
Results to CScore allows you to relax the protein/ligand complex
Extract in various ways. Scores can be generated before and/or
after such relaxation. This dialog can work with either
set. Sets lacking data remain greyed out.

Select Best Docked Solution by Score

You may define the criteria used to select a single ligand pose (conformation/
orientation) from the set provided by a docking program.
It is possible that some protein/ligand pairs will not have a pose which meets
the specified consensus and score criteria. Such pairs will be ignored.
Consider several selection mechanisms in the following example: four poses for
a single ligand, scored by three scoring functions.
Score X Score Y Score Z Consensus
Pose_1 -5.4 -3.2 -97 3

Pose_2 -2.2 -2.2 -23 0
Pose_3 -5.2 -2.4 -45 1
Pose_4 -4.5 -1.8 -105 2
Consensus Scoring Pose Selected Reason

Criterion Function
Consensus >= 3 any single func- Pose_1 Pose_1 is the

tion or any only pose with a
combination consensus of at
least 3.
Consensus >= 2 Score Z Pose_4 Pose_4 has a
consensus of at
least 2 and is
ranked as best by
function Z
Consensus >= 0 Score X Pose_1 Pose_1 is ranked
as best by func-
tion X.
Consensus >= 0 Score Z Pose_4 Pose_4 has a
consensus of at
least 2 and is
ranked as best by
function Z

Consensus Scoring Pose Selected Reason

Criterion Function
Best Consen- Score Y Pose_1 Pose_1 has the
sus>=2 highest consen-
sus score and is
ranked as best by
function Y.
Best Consen- Score Z Pose_1 Pose_1 has the
sus>=2 highest consen-
sus score and is
ranked high by
function Z.
Consensus Cri- The consensus scores of the protein/ligand pairs is used

terion to select a pose. This criterion is combined with the
Single Function or defined Multi-Function.
• Consensus >= Identifies all poses with a
consensus score equal to or bigger than the value in
the adjacent menu, then selects among them the
pose with the best score as ranked by the selected
Single Function or defined Multi-Function. The
default, 0, guarantees that one conformation will be
selected for each ligand; the one ranked highest by
the selected scoring function.
• Best Consensus >= starts by identifying all
poses with a consensus score equal to or bigger than
the value in the adjacent menu. This option differs
from the other in that for each ligand, docked
solutions with the highest consensus value are
given preferential treatment. The selected Single
Function or defined Multi-Function then deter-
mines among those which solutions are extracted.
If, for a particular ligand, no pose has the desired con-
sensus value, the ligand is dropped.

Single Function The solution with the best value of the specified CScore
scoring function will be selected. The menu indicates
which of D_score, PMF_score, G_score, ChemScore
and Total_score are present and thus selectable.
Assuming that a force field-like function selects the
best pose (docked conformation) for each ligand,
D_score or G_score or a combination of both are proba-
bly most appropriate for this type of selection. Because
PMF_score does not include the hydrogens, it is not
recommended here.
Multi-function The solution with the best value of the user-specified
Define weighted function of CScore scores will be selected.
The CScore Define Function dialog is used to define
this function.
Extract Ligand Subset

To extract a set of ligands (from those defined above) meeting various criteria.
Overall Consen- The consensus value is generated from the scores for all
sus ligands selected by the Select Best Docked Solution by
Score criteria, using the user-specified CScore scoring
functions. A check box is provided for each score
which is present in the input data, so you may select
those to be included. Scores missing from the input data
are greyed out
Extract by To determine which ligands will be extracted. The valid
range for the selected options is indicated beside the
field box.
• Top N—The best N ligands will be extracted. The
allowed range is from 1 to the number of ligands
that pass the Select Best Docked Solution by Score
criteria).
• Top Pct—The best x.x percent of the ligands will
be extracted. The allowed range is 1–100.
• Consensus >=—All ligands with an overall
consensus equal to or greater than the specified
value will be extracted.
Checking Extract by activates Single Function and
Multi-function.

Single Function The subset with the best values of the specified CScore
scoring function will be selected. The menu indicates
which of D_score, PMF_score, G_score, ChemScore
and Total_score are present and thus selectable.
The Single Function radio button is accessible only if
the Extract by check box has been activated.
Multi-function The subset with the best value of the user-specified
Define weighted function of CScore scores will be selected.
The CScore Define Function dialog is used to define
this function.
The Multi-function radio button is accessible only if
the Extract by check box has been activated.
Output Options
Output Prefix Enter the prefix to be used when creating output files:
• a text output file (.out) containing information
suitable for importing into a spreadsheet;
• files containing the extracted ligands meeting all
criteria. A file or directory is created for each of the
requested output formats.
If the path information is omitted, the files are written
in the current directory. If files from a previous run are
present, you will be asked whether they should be over-
written. If you indicate that new files are desired, file-
names of the form prefix_n will be used, where n is the
lowest unique integer (starting at 1).
Output Details Access the CScore Output Details dialog. Use it to
select the format of the output file(s).
Delimiter Whether the text output file will be written with
Space, Comma or Tab column delimiters.
Extract by Selected Matched Optional Pharmacophore Constraints

No longer supported.
3.3.1 Define the CScore Function

To define a weighting function for the various scores used to evaluate whether
protein-ligand complexes will be extracted.

In the CScore Subset Extraction dialog, press either of the Multi-function
Define buttons.

Weight Enter a weight for each score present in the input data
(missing scores are greyed out). These can be positive
or negative numbers.
OK Apply the specified weights to the scoring functions.
The resulting function is displayed in the CScore Subset
Extraction dialog for reference.
3.3.2 Select the CScore Output Formats

To select the format of the CScore output file(s) containing the extracted
ligands.

In the CScore Subset Extraction dialog, press Output Details.
Output Formats Select one or more file formats to save the extracted
ligand poses.
• Multi-Mol2—A single .mol2 file containing all the
extracted ligand poses.
• SLN File—A file in SLN format (.hits) that also
includes the scores.
• SD File—A file in MDL data format (.sdf) that
also includes the scores
• Spreadsheet—A spreadsheet of the extracted
ligand poses with their scores. You may save the
spreadsheet to a table file (.tbl).

4. Run CScore via the Command Line
• SYBYL Command: CSCORE on page 28
• CScore Standalone Utility on page 29
• Initial Setup on page 29
• Simple Operation on page 29
• One-Molecule Operation on page 30
• One-Directory Operation on page 30
• Surflex-Dock Job Directory on page 30
• CScore Runfile on page 31
• Working With Metal Atoms on page 31

SYBYL Command: CSCORE
4.1 SYBYL Command: CSCORE

To create a number of new columns, each containing a particular score for the
protein/ligand docked result.
Licensing: See License Requirements for CScore on page 7.
Menubar: MDE: CScore

Command: CSCORE filename row_expr
• filename—Name and path to the Mol2 file
containing the receptor molecule to be associated
with the spreadsheet. The ligands in the rows were
docked into the active site of this receptor.
• row_expr—Rows to be used in consensus scoring.
By default, all rows are selected.
The CSCORE command works with spreadsheets containing docked results for a
single ligand or multiple ligands. This is determined by the parameter
independent_ligands in the file $TA_MOLTABLES/cscore.par.
This parameter sets the appropriate table attributes when run. So if you save the
spreadsheet with the scores into a table file (.tbl), you can later open it in menu
mode, and the CScore menu will be automatically posted in the spreadsheet.
• Run CScore via the Menubar on page 15
• Tailor subject CSCORE to customize the parameters used to compute the
consensus column (in the Tailor Manual)
• TABLE CONSENSUS (in the Molecular Data Explorer Manual)

CScore Standalone Utility
4.2 CScore Standalone Utility

CScore can be run standalone outside of the SYBYL application. Several modes
of operation are described below, along with the appropriate command lines.
4.2.1 Initial Setup

Define the Environment in a System Shell:
! Refer to SYBYL-X Environment Shell in the SYBYL Basics Manual.
Parameter File:
Use $TA_MOLTABLES/cscore_exe.par as a starting point for making your
own parameter file. See CScore Parameters on page 45 for details.
Note: cscore_exe assumes that you are doing a one-directory operation. If you
are doing any other operation, be sure to include the appropriate parameters for
that type of operation.
Operation Mode:
The operation mode that is used by CScore is controlled by the parameter
operation_mode. The default value (cscore_runfile) in the parameter file is
designed for use only with the graphical interface. To run from the command
line, copy the default parameter table to your working directory. Change the
operation_mode as described below and make other changes as needed. Then
specify this modified parameter table on the command line.
4.2.2 Simple Operation

To work with a simple protein/ligand pair:
! Review the Initial Setup instructions above.
! Type: $TA_BIN/CScore protein par_file ligand

• Do not include extensions when entering file names.
• In the parameter file, set the operation_mode parameter to simple.
• Both protein and ligand are .mol2 files, and CScore assumes that they
share a common coordinate system. If optimization is performed,
ligand.new (and protein.new if appropriate) are created with the new
coordinates.
• If CScore scores are requested, ligand.cso contains the scores.

4.2.3 One-Molecule Operation

To optimize selected torsional angles in a single file:
! Type: $TA_BIN/CScore filename par_file

• Do not include extensions when entering file names.
• In the parameter file, set the operation_mode parameter to one_mol.
• As above, optimization yields a filename.new file with the new coordi-
nates. No CScore scores can be calculated as there is no explicit protein/
ligand association. If you wish to work with a single .mol2 file
containing a protein/ligand pair, you should use the TORSMIN command.
4.2.4 One-Directory Operation

To work with all Mol2 files in a single SYBYL database:
! Type $TA_BIN/CScore protein par_file directory
Do not include extensions when entering file names.
In the parameter file:

• set the operation_mode parameter to one_dir.
• set the independent_ligands to no if the directory contains different
conformations of the same molecule.
• set the independent_ligands to yes if the directory contains different
molecules.
Optimization yields a new Mol2 database with the name directoryr.mdb,

containing all the optimized ligands in individual .mol2 files.
CScore scores can be calculated for the initial and/or optimized structures,
creating a directory.cso and/or directoryr.cso file as appropriate. This mode is
used when calling CScore from within the docking calculation.
4.2.5 Surflex-Dock Job Directory

To perform CScore calculations on a Surflex-Dock output job directory:
! Go to the Surflex-Dock job directory.

! Identify the file (jobname.file_names) containing the list of ligand

.mol2 files used in the Surflex-Dock run. The file cannot be used as is
by CScore. All the .mol2 extensions must be removed.
! Type the following command, replacing jobname as appropriate to
create a new file for use by the CScore command:
sed 's/\.mol2//g' jobname.file_names > cscore.file_names
! Type: $TA_BIN/CScore protein par_file cscore

• protein is the protein .mol2 file in the job directory.
• In the parameter file, set the operation_mode parameter to flexx_jobdir.
• cscore is the basename of the cscore.file_names file created
above.
• Optimization yields a .cso file (ligand_filename.cso and ligand_
filenamer.cso if appropriate) containing the scores for all ligands and
poses.
4.2.6 CScore Runfile

This mode is used by the CScore graphical interface and command. It is
documented here for completeness.
! Type: $TA_BIN/CScore protein par_file CScore_runfile

• In the parameter file, set the operation_mode parameter to cscore_
runfile.
• When run from a molecular spreadsheet outside Surflex-Dock, the
CSCORE command might need to create directories to hold temporary
files, along with the results of structure relaxation (if requested). This
mode enables the CScore program to correctly interact with SYBYL’s
CSCORE command.
4.2.7 Working With Metal Atoms

If the protein includes metal atoms, their valences must be filled with dummy
(DU) atoms in the input .mol2 file to the CScore command.
If you need to modify parameters use the following directions.

1. Create a new directory to hold your copy of these parameters in text format.
In the following instruction, replace new_directory with the name of a new
directory of your choice.

! Type: PARAMETER ASCII WRITE new_directory

2. Outside of SYBYL, copy the following files from $TA_ASCTABLES to the
newly-created directory:
• PMF_Ligand.rules
• PMF_Protein.rules
• pmf.tab
• ChemScore.rules
• GScore.rules
• DOCK_VDW
To inform CScore where the parameter files are:

1. Change the environment variable TA_ASCTABLES to point to the directory
created above.
2. Add a line to the end of the CScore parameter file of the form
TA_ASCTABLES new_directory/
where new_directory is the name of the newly-created directory.
If you have or wish to change the parameter files for the charge estimation
routines, look in $TA_MOLTABLES for the original copies. These, too, can be
copied (and modified) in the newly-created directory. You must then inform
CScore of the location of your files.

5. CScore Theory
• Purpose of CScore on page 34
• CScore Input Requirements on page 35
• Generating a Consensus on page 36
• G_Score on page 37
• PMF_Score on page 39
• D_Score on page 40
• ChemScore on page 41
• Total_Score on page 43
• CScore Suggested Reading on page 44

5. CScore Theory
Purpose of CScore
5.1 Purpose of CScore

Docking of small molecules into their biomolecular receptors is a useful tool in
many areas of computational drug design. This is an active area of research, and
a reasonable number of alternatives are available. These differ on implemen-
tation details: flexible vs. rigid ligands, whole-molecule vs. incremental
construction, flexible vs. rigid protein, etc. But all rely on a scoring function to
evaluate the placement (and possibly conformation) of the ligand-protein pair.
Scoring functions can be adapted from force field approaches, estimating the
enthalpy of binding via the pair-energy of the complex. Other functions estimate
the entropy of binding, incorporating terms for desolvation and loss of confor-
mational flexibility. While such functions are more chemically appealing, they
require significantly more statistical fitting than those based on force fields.
Statistically-fit functions are dependent on their training set. Each author has
tried to make this as general as possible, but concerns remain as to the extensi-
bility of these functions to new systems. Since each scoring function has been
derived from a different set of crystal structures, it is reasonable to use multiple
functions when evaluating a protein-ligand pair. A consensus can be
developed—structures which are considered good fits in multiple scoring
functions can be examined further, while those which do not can be dropped.
A publication by Tripos scientists validates the CScore™ approach to consensus

scoring in virtual high throughput screening [Ref. 6].

5. CScore Theory
CScore Input Requirements
5.2 CScore Input Requirements

You must have a protein target, and a collection of docked ligands all sharing a
common coordinate system. The structures must have filled valences, extra-
neous atoms removed and correct atom and bond types. The ligands will be
contained in a molecular spreadsheet, and the protein will be defined as an
attribute of that spreadsheet.
CScore provides several functions:

• G_score, based on the work of Willett’s group [Ref. 1]
• D_score, based on the work of Kuntz et al [Ref. 3]
• PMF_score, based on the work of Muegge and Martin [Ref. 2].
• ChemScore, based on the work of Eldridge, Murray, Auton, Paolini, and
Mee [Ref. 4].
The consensus can be generated from any combination of these or other previ-
ously-calculated scores.

5. CScore Theory
Generating a Consensus
5.3 Generating a Consensus

The consensus score is the sum of the number of “good” results for each ligand
(row) in each scoring function (column). The range of scores for each scoring
function are determined, normalized (ranging from 0 to 1), and all values above
the cutoff threshold are considered good. By default, the lower half of the
normalized scores is discarded. A simple example follows:
Score A Score B Consensus
Ligand A -5.4 -3.2 2

Ligand B -2.2 -2.2 0
Ligand C -5.2 -2.4 1
Ligand A has a “good” score for both functions, while Ligand B has a “bad”
score for both functions. The results for Ligand C are ambiguous, and further
examination is suggested.
“Good” is determined by calculating the range of the scores, then taking the
compounds in the top fraction of the range as determined by the value set by
Tailor variable CSCORE FRACTION.
As mentioned above, the protein and all ligands must share a coordinate system.
The molecular spreadsheet can contain different results for a single ligand, or it
can contain results for a number of ligands (user-generated).

5. CScore Theory
G_Score
5.4 G_Score
This scoring function is drawn from the work of Willett’s group [Ref. 1], using
the hydrogen bonding, complex (ligand-protein), and internal (ligand-ligand)
energies.
5.4.1 Complex Energy
 A B
E complex = ∑ ∑  r----8- – ----
-
4

[EQ 1]
lig prot ij r ij
where:
• rij is the interatomic distance
• A and B are obtained from the Tripos force field parameters for each
atom type
• All terms are limited to [-0.5, 0.5] to prevent atoms in close proximity
from overpowering the calculation. This is softer than the common 6-12
potential and favors close contacts between hydrophobic moieties.
5.4.2 Internal Energy
E int = E vdw + E tors [EQ 2]

where:
• Etors is the torsional energy of the Tripos force field
• Evdw is given by:
C D
E vdw = ∑ ∑  ------
r
12
- – -----
r 
6
[EQ 3]
i j ij ij
where:
• C is chosen so that Eij is at a minimum when the atom pair is separated
by the sum of their van der Waals radii.
• Dij is given by:
3 Ii Ij αi αj
– --- ( 0.23 ) ------------------ [EQ 4]
2 Ii + Ij
where:
• Ii is the ionization potential

5. CScore Theory
G_Score
• αi is the centered polarization for atom type i.
5.4.3 Hydrogen Bonding Energy

The hydrogen bonding energy is a complex function based on the atom types
and geometries of bond pairs (including metal interactions). See Ref. 1 for a
complete description.
5.4.4 Special Notes

To obtain score values consistent with the published scoring function, you must
define all ligand bonds as rotatable. Note, however, that if you don’t, the
scoring values will still be consistent internally and provide all necessary infor-
mation for use with consensus scoring.
See the use_bonds_lig, relax_structure and rigid_structure parameters in CScore

Parameters on page 45.
The G-score scoring function gives qualitatively different results depending on

whether the structure has a Kékulé or an aromatic representation.

5. CScore Theory
PMF_Score
5.5 PMF_Score
This scoring function is drawn from the work of Muegge and Martin [Ref. 2],
who analyzed a large set of complexes drawn from the Protein Data Bank and
developed a set of Helmholtz free energies of interactions for protein-ligand
atom pairs (Potential of Mean Force, PMF).
PMF score = ∑ ∑ Aij rij [EQ 5]

i j
where:
• Aijrij = the contribution of a pair of atoms of type i and j at a distance rij.
These were obtained from the tabulated PMF functions, and implicitly treat the
various enthalpic, entropic, and solvation effects. A cutoff of 12 Å was used
when deriving the PMF’s. A cutoff of 9 Å for non carbon interactions and 6 Å
for carbon interactions is used for scoring. All hydrogen atoms are ignored.
Note: Dr. Muegge improved the scoring function after the original publication
[Ref. 2]. These improvements are reflected in the Tripos implementation of
PMF_Score.

5. CScore Theory
D_Score
5.6 D_Score
This scoring function is drawn from the work of Kuntz and al. [Ref. 3], using
only the charge and van der Waals interactions between the protein and the
ligand:
A B qi qj
D score = ∑ ∑  r12 r6
 ------
- – ----- + 332.0 -
---------
Dr ij
[EQ 6]
lig prot ij ij
where:
• qi is the charge of atom i
• D is the dielectric constant
• A and B are obtained from the Tripos force field parameters for each
atom type
• Charges are computed by the Gasteiger-Marsili method
• The van der Waals term is ignored for hydrogen bonding hydrogens
• All terms are limited to [-0.5, 0.5] to prevent atoms in close proximity
from overpowering the calculation.
The receptor file has hydrogens added, lone pairs removed, and any Mg, Ca,
Mn, Fe, Co or Zn ions are bonded to all atoms within 3.5 Å. Formal charges for
metals are derived from information in $TA_DATA/sybyl.tpd. Charges for
Mg, Ca, Mn, Co, and Zn are set to +2. The CScore parameter file determines
whether Fe has a charge of +2 or +3.

5. CScore Theory
ChemScore
5.7 ChemScore
This scoring function is based on the work of Eldridge, Murray, Auton, Paolini,
and Mee [Ref. 4]. It includes terms for hydrogen bonding, metal-ligand inter-
action, lipophilic contact, and rotational entropy, along with an intercept term.
5.7.1 Hydrogen Bonding Energy
∆G HBond = ∑ ∑ g1 ( ∆r )g2 ( ∆α ) [EQ 7]

Lig Prot
where: 1 if ∆r ≤ 0.25Å

• g 1 ( ∆r ) = 11– ( ∆r – 0.25 ) ⁄ 0.4 ifif∆α < ∆r ≤ 0.65Å
≤ 0.25Å
0.25Å

• g 2 ( ∆α ) = 01 – ( ∆α – 30 ) ⁄ 50 ∆r <> ∆α
ifif30° ≤ 80°
0.65Å

if ∆α
These are the same 0functional forms used by Böhm> 80°
[Ref. 5] to estimate
∆Gbinding.
5.7.2 Metal-Ligand Energy
∆G Metal = ∑ ∑ f ( ΓiM ) [EQ 8]

Lig Prot
where:
• ΓiM = the distance
1 Γ iM ≤
between the ligandifatom 2.2Å
and the metal atom

• f ( Γ iM ) =  1 – ( Γ iM – 2.2 ) ⁄ 0.4 if 2.2Å < Γ iM ≤ 2.6Å

0 if Γ iM > 2.6Å
5.7.3 Lipophilic Contact Energy
∆G Lipo = ∑ ∑ f ( ΓiI ) [EQ 9]

Lig Prot
where:
• ΓiI = the distance between the lipophilic ligand atom i and the lipophilic
proton atom  1 I. if Γ iI ≤ R 1 Å

• f ( Γ iI ) =  1 – ( Γ iI – R 1 ) ⁄ 3.0 if R 1 Å < Γ iI ≤ ( R 1 + 3.0 )Å

• where: 0 if Γ iI > ( R 1 + 3.0 )Å
• R1 = vdW(i) + vdW(I) + 0.5

5. CScore Theory
ChemScore
5.7.4 Rotational Energy
P nl ( i ) + P' nl ( i )
∆G Rot = 1 +  1 – -----------
1
N Rot ∑ ------------------------------------
2
[EQ 10]
Bonds
where
Pnl(i) and P’nl(i) are the fraction of non-lipophilic atoms on either side of
the frozen bond. Only single bonds are considered. Bonds are considered
frozen if atoms on both sides of the rotatable bond are in contact with the
receptor.
5.7.5 Special Notes

To obtain score values consistent with the published scoring function, you must
define all ligand bonds as rotatable. Note, however, that if you don’t, the
scoring values will still be consistent internally and provide all necessary infor-
mation for use with consensus scoring.
See the use_bonds_lig, relax_structure and rigid_structure parameters in CScore

Parameters on page 45.

5. CScore Theory
Total_Score
5.8 Total_Score
CScore always reports the output of the docking engine as TOTAL_SCORE
(See License Requirements for CScore on page 7).
Surflex-Dock was developed by Prof. Ajay N. Jain, University of California San

Francisco (UCSF) and BioPharmics LLC.
See also the SYBYL Docking Suite.

5. CScore Theory
CScore Suggested Reading
5.9 CScore Suggested Reading

[1] G. Jones, P. Willett, R. Glen, A.R. Leach and R. Taylor, J. Mol. Biol.,
1997, 267, 727
[2] I. Muegge and Y. C. Martin, J. Med. Chem., 1999, 42,791
[3] I. D. Kuntz, J. M. Blaney, S. J. Oatley, R. Langridge, and T. E. Ferrin, J.
Mol. Biol., 1982, 161, 269
[4] M. D. Eldridge, C. W. Murray, T. R. Auton, G. V. Paolini, and R. P.
Mee, J. Comp.-Aided Molec. Des., 1997, 11, 425-445
[5] H.-J. Böhm, J. Comp.-Aided Molec. Des., 1994, 8, 243
[6] R.D. Clark, A. Strizhev, J. M. Leonard, J. F. Blake, and J. B. Matthew,
“Consensus scoring for ligand/protein interactions” J. Mol. Graph.
Mod., 2002, 20, 281.
[7] Renxiao Wang, Yipin Lu,and Shaomeng Wang, “Comparative
Evaluation of 11 Scoring Functions for Molecular Docking” J. Med.
Chem. 2003, 46, 2287-2303.
Validation
A publication by Tripos scientists validates the CScore™ approach to consensus
scoring in virtual high throughput screening:
R.D. Clark, A. Strizhev, J. M. Leonard, J. F. Blake, and J. B. Matthew,
“Consensus scoring for ligand/protein interactions” J. Mol. Graph. Mod.,
2002, 20, 281.

6. CScore Parameters
The CScore parameters are used slightly differently by various SYBYL

functions:
• The Docking graphical interface, when CScore calculations are
requested, uses the parameters stored in the file $TA_MOLTABLES/
flexx_cscore.par. This file is customized to take into account that all
ligands are instances of the same molecule (independent_ligands = no)
and that the docking engine will be calling CScore one ligand at a time
(operation_mode = one_dir). In addition, the values of the options in the
CScore Details dialog are appended. You can specify a different
parameter file in this dialog if desired.
• The CSCORE command uses the parameters stored in the file
$TA_MOLTABLES/cscore.par. By default, the parameters in this file
assume a set of different ligands docked into the same receptor
(independent_ligands = yes) and that Cscore is being used from within
SYBYL (operation_mode = cscore_runfile). You can specify a different
parameter file via Tailor variable CSCORE PARAMETER_FILE if
desired.

6.1 CScore Parameters: $TA_MOLTABLES/cscore.par
46
CScore Parameters: $TA_MOLTABLES/cscore.par

Default values appear in bold in the table below.
CScore
Parameter Options Meaning
use_non_rot_prot yes | no To include/exclude non-single bonds of the protein

during optimization.
use_amide_prot yes | no To include/exclude protein amide bonds during
optimization. use_non_rot_prot overrides
use_amide_prot.
use_backbone_prot yes | no To include/exclude backbone atoms of the protein
during optimization. Warning: This option can sig-
nificantly alter protein geometry.
use_bonds_prot all | none | honly | defined To specify which torsions should be optimized.
HONLY refers to all X-X-X-H torsions, DEFINED
refers to those defined in the
FLEXIDOCK_BONDSa bond set.
use_non_rot_lig yes | no To include/exclude non-single bonds of the ligand
use_amide_lig yes | no To include/exclude ligand amide bonds during opti-
mization. use_non_rot_lig overrides use_amide_lig.
use_backbone_lig yes | no To include/exclude backbone atoms of the ligand
SYBYL-X 2.1
during optimization. Set this parameter to YES for

peptidic ligands you want optimized.
SYBYL-X 2.1
CScore
use_bonds_lig all | none | honly | defined To specify which torsions should be optimized.
HONLY refers to all X-X-X-H torsions,
DEFINED refers to those defined in the
FLEXIDOCK_BONDSa bond set. The literature has
not resolved whether full or rigid ligand optimiza-
tion is best for CScore calculations at this time.
Note: For the G_score and ChemScore functions,
use all bond ligands to obtain results consistent with
the published scoring functions. See also the
relax_structure and rigid_structure parameters.
use_dist_dep_diel yes | no To switch between distance-dependent and con-
stant dielectric functions.

use_charges yes | no Whether to use partial charges during optimization.
use_torsionals yes | no Whether to use the torsional energy term during
optimization.
use_constraints yes | no (currently not available)
use_rt yes | no Whether ligand rotation and translation can be per-
formed during optimization.
use_vdw yes | no Whether to use the VdW energy term during opti-
mization. This parameter is included for complete-
ness. You should be careful when turning off VdW
CScore
energies.
diel_const x.x <1.0> To specify the dielectric constant.
47
48

bfgs_print yes | no | debug To turn on various output levels during optimiza-

CScore
tion.
max_cycles n <100> To specify the maximum number of optimization
cycles.
max_line_tries n <10> To specify the maximum number of line-minimiza-
tion tries.
print_interval n <10> To specify the number of optimization cycles
between information printouts. bfgs_print, natu-
rally, overrides this parameter.
initial_alpha x.x <0.001> To specify the initial value of alpha, the line-mini-
mization stepsize.
max_alpha x.x <1.0> To specify the maximum value of alpha.
alpha_multiple x.x <10.0> To specify the stepsize for alpha during line mini-
mization (each new alpha is <alpha_multiple> times
larger than the previous).
alpha_tolerance x.x <0.1> To specify the tolerance for the line-minimization
process.
grad_tolerance x.x <0.01> To specify the gradient cutoff parameter.
dist_tolerance x.x <0.01> To specify the displacement cutoff parameter.
SYBYL-X 2.1
energy_tolerance x.x <0.1> To specify the energy cutoff parameter. CScore uses
a larger-than-usual value to terminate optimization
quickly.
SYBYL-X 2.1
CScore
min_e none | x.x To terminate optimization when the energy drops
below this value. min_e is different from
energy_tolerance, which measures the energy dif-
ference between successive iterations.
hess_update x.x <10-7> To specify the threshold below which the hessian
matrix will be reinitialized during optimization.
grad_step x.x <0.01> To specify the stepsize for the numerical torsional
derivatives (in radians).
max_displace x.x <1.0> To specify the maximum ligand displacement (in Å)
for a single optimization step. It can be used to try
an keep ligands in “cluttered” clefts.

tr_h_vdw_radius large | small | split | x.x To specify the VdW radius for hydrogen.
LARGE uses 1.5 Å, SMALL uses 1.0 Å.
SPLIT uses LARGE hydrogen atoms in the 1-4
VdW energy term and SMALL hydrogen atoms in
the non- bonded VdW energy term.
tr_h_vdw_epsilon hard | soft | split | x.x To specify the VdW epsilon for hydrogen.
HARD uses 0.042, SOFT uses 0.030.
SPLIT uses HARD hydrogen atoms in the 1-4 VdW
energy term and SOFT hydrogen atoms in the non-
bonded VdW energy term.
CScore
tr_hb_factor x.x <0.7> To scale the VdW radii for H-bonding atom pairs
(thus allowing them to be closer without VdW
energy penalties) during optimization.
49
50

tr_14_scale x.x <1.0> To scale the contribution from the 1-4 energy terms
CScore
forcefield tripos (Only supported FF at this time)
TA_ASCTABLES directory To specify where the data files for optimization and
CScore scores are located if the directory pointed to
by the environment variable TA_ASCTABLES is
inappropriate.
TA_MOLTABLES directory To specify where the data files for the charge calcu-
lations are located if the directory pointed to by the
environment variable TA_MOLTABLES is inap-
propriate.
relax_structure yes | no To relax the designated torsionals (and ligand, if
specified). If protein sidechain torsionals are
included, a protein file named P_<ligand-filename>
is written with the new coordinates. Care should be
taken when relaxing protein sidechains, as it can
create a large amount of data.
see also the use_bonds_lig and rigid_structure
parameters.
rigid_structure yes | no To ignore all defined torsional angles if rigid-body
docking is desired.
SYBYL-X 2.1

see also the use_bonds_lig and relax_structure
parameters.
SYBYL-X 2.1
CScore
independent_ligands yes | no Whether the ligands in a SYBYL database or
spreadsheet have the same or different chemical
structures.
initial_cscore yes | no To generate CScore scores for the initial docked
structures.
final_cscore yes | no To generate CScore scores for the final optimized
structures.
cscore_D_score yes | no To include the D_SCORE function.
cscore_PMF_score yes | no To include the PMF_SCORE function.
cscore_G_score yes | no To include the G_SCORE function.

cscore_Chemscore yes | no To include the ChemScore function.
prot_charge delre | gasteiger | gasteiger-pi | To specify which partial charge model should be
huckel | gast-huck | pullman | used for the protein. use_charges overrides this
use_current | none parameter.
lig_charge delre | gasteiger | gasteiger-pi | To specify which partial charge model should be
huckel | gast-huck | pullman | used for the ligand. use_charges overrides this
use_current | none parameter.
operation_mode simple | one_mol | flexx_jobdir | To specify the operation mode for CScore. This is
cscore_runfile | one_dir usually set based on the particular command and/or
CScore
GUI being used.

Fe_charge x.x <2.0> To specify the formal charge for iron atoms, and
must lie in the range 2.0–3.0
51
52

dscore_epsilon x.x <4.0> To specify the dielectric constant for the D_SCORE
CScore
calculation.
dscore_cutoff none | x.x <20.0> To specify the distance cutoff for the D_SCORE
calculation.
dscore_exponents n n <6 12> To specify the VdW A and B exponents for the
D_SCORE calculation.
dscore_max_contrib none | x.x <0.5> To specify the maximum contribution for an atom-
pair in the D_SCORE calculation. It is set relatively
low to prevent bad contacts from dominating the
score.
dscore_dist_dep_diel yes | no To specify whether distance-dependent or constant
dielectric function is used in the D_SCORE calcula-
tion.
dscore_dock_params yes | no To switch between parameters drawn from the Tri-
pos forcefield or the Dock tabulated parameters.
PMF_use_12 yes | no To switch between a 12 Å cutoff and the 6/9 Å cut-
offs described in the PMF literature.
gscore_max_contrib none | x.x <0.5> To specify the maximum contribution for an atom-
pair in the G_SCORE calculation. It is set relatively
low to prevent bad contacts from dominating the
score.
SYBYL-X 2.1
gscore_h_cutoff x.x <7.0> To specify the cutoff distance (in Å) for the H-bond
term in the G_SCORE calculation.
SYBYL-X 2.1
CScore
gscore_c_cutoff x.x <9.0> To specify the cutoff distance (in Å) for the com-
plex term in the G_SCORE calculation.
gscore_s_cutoff x.x <12.0> To specify the cutoff distance (in Å) for the steric
term in the G_SCORE calculation.
chemscore_waters yes | no To specify whether crystallographic waters in con-
tact with the protein should be used in the Chem-
Score calculation.
chemscore_debug yes | no To generate debugging information in the Chem-
Score calculation, and is intended to be used when
validating this score.
a. The FLEXIDOCK_BONDS set is used by Torsmin and CSCore to identify the rotatable bonds in the current Mol2 file. This is the

maximum number of rotatable bonds which will be used in the calculation, as ring torsionals are not handled at this time. Terminal bonds are
ignored, and non-single bonds are included or excluded based on user selections in the parameter file.
CScore
53
CScore Index
B F
Bibliography Files created
CScore 44 CScore 24, 25
C G
ChemScore function 41 G_Score function 37
Command
descriptions L
CScore 28
License requirements
Consensus
CScore 7
and best consensus 21
scoring
definition 36 M
introduction 5
selecting the best docked solution 21 Metals
within a spreadsheet 18 in CScore 31
CScore Molecular Spreadsheet
best solution 21 Cscore 18
bibliography 44
ChemScore 41
command outside SYBYL 29
P
command within SYBYL 28 Parameters 45
consensus and best consensus 21 PMF_Score function 39
consensus definition 36
Protein modeling
D score 40
scoring methods 33
extraction 20
F Score 43
G Score 37 R
graphical user interface 15
introduction 5 References
menu 18 CScore 44
operation mode 29
parameters 45 S
PMF score 39
purpose 34 Scoring methods
requirements 35 protein modeling 33
running while docking 16 Standalone utilities
selecting the scoring functions 16 CScore 29
standalone utility 29
subset extraction 20
theory 33 T
tutorials 9 Tutorials
using within a spreadsheet 18 CScore 9
working with metal atoms 31
D
D_Score function 40

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CScore™ Manual

1699 South Hanley Rd. Phone: +1.314.647.1099

3. Run CScore via the Menubar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

4. Run CScore via the Command Line . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

SYBYL-X 2.1 CScore 3

CScore (Consensus Score) integrates a number of popular scoring functions for

CScore can be run in a number of ways:

SYBYL-X 2.1 CScore 5

1.1 What is New with CScore

CScore Subset Extractor

MDBs are no longer supported as input or output options for CScore. As a

Docking Properties in Results Spreadsheet

6 CScore SYBYL-X 2.1

1.2 License Requirements for CScore

SYBYL-X 2.1 CScore 7

The exponential increase in the number of protein crystal structures available

SYBYL-X 2.1 CScore 9

2.1 CScore and Surflex-Dock in SYBYL

The Surflex-Dock graphical user interface (described in the Docking Suite

10 CScore SYBYL-X 2.1

2.2 Using CScore with Externally-Generated

A Matter of Time: This tutorial requires a couple of minutes of personal time.

2.2.1 Retrieve the Spreadsheet and Associated Receptor

! > Delete Everything

! Click to reset all rotations and translations.

2. Open the spreadsheet containing the docking results.

! Click on the SYBYL toolbar.

! Set Files of Type to Spreadsheet.

! Select [$TA_DEMO] in the Bookmarks list then double-click

The spreadsheet is displayed. It contains the extracted ligand and the 10

3. Check the spreadsheet’s ORIGIN attribute.

! In the command console type: table attribute list origin

The console reports: DOCKING.

SYBYL-X 2.1 CScore 11

4. Identify the Mol2 file containing the associated protein, carboxypeptidase A.

! MDE: CScore > Set Receptor

! Select [$TA_DEMO] and docked_receptor.mol2 then press OK.

2.2.2 Run CScore

Run CScore With Rigid Ligands

! MDE: CScore > Run CScore

CScore proceeds and adds five score columns to the spreadsheet.

Run CScore With Relaxed Ligands

! Delete the five columns created by the CScore run.

8. Run CScore again.

! In the CScore dialog toggle on the option to Relax Molecules and

12 CScore SYBYL-X 2.1

9. Compare the two CScore columns: CSCORE (unrelaxed) and CSCORER

2.2.3 Final Notes

! MDE: File > Close

! Press No at the prompt to save it to a table file.

SYBYL-X 2.1 CScore 13

SYBYL-X 2.1 CScore 15

3.1 Run CScore while Docking

Licensing: See License Requirements for CScore on page 7.

Applications > Docking Suite > Dock Ligands

The Docking dialog is described in the Docking Suite Manual.

See the CScore Theory on page 33 for a description of available scoring

3.1.1 CScore Details

16 CScore SYBYL-X 2.1

SYBYL-X 2.1 CScore 17

3.2 Use CScore in a Spreadsheet

Spreadsheet of Surflex-Dock results:

If the spreadsheet contains the results of another docking program: