Working with FRED 2'0

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Working with FRED 2.0

• What the hell did you change, Mark?

Steve grammar checker
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Versioning

• Version of the following form M.m.b
• M major version
• Major changes in internal code structure
• m minor version
• Feature changes
• New parameters, parameter changes
• b bugfix version
• Bugfixes, no feature change
• Beta
• Few if any feature changes
• bugfixes

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Vs. Fred 1.2.10

• Number of Parameters
• Fred 1.2.10 78
• Fred 2.0b 25
• So whats missing
• Parameters no on uses (e.g., -bb, -cube_scr)
• Collapsed many parameters into single best case
• ScreenA,B,C are gone
• On the fly conformer generation
• No shape free energy (i.e.,-temp and Eo)
• No screenscore (may be in final release)

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So why do I want to use Fred 2.0b?

• OEChemplete
• New Scoring Functions
• ChemGauss
• Zap Bind
• Scoring Methodology
• Chemical perception exhaustive search
• M.A.S.C.
• Documentation
• Faster (30-50)
• Less memory

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Input Parameters

• Ligand Database
• -dbase (-db) File with ligands
• -scdbase (-combine_conf) Flag to combine
• Active Site
• -pro Target protein
• -box Box enclosing active site
• -addbox Parameter to extand box

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Output Parameters
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Docking methodology

• Generate initial ensemble of poses
• Filter Negative Image
• Filter Constraints
• Score
• Shape (Gaussian Scoring Function)
• PLP
• ChemGauss
• Rescore
• Chemscore
• Zap Bind
• MASC Correction

Optional
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Pose GenerationSome things never change
Rotations
Translations
rstep
tstep
Relevant Parameters -tstep translational
step size (default 1.0Å) -rstep
rotational step size (default 1.5Å)
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Filter - Negative Image
Negative image
protein
Relevant Parameters -clash_checking
strict, normal, loose (formally excrad)
-neg_img_size small, normal, large,
xlarge (formally excvol)
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Constraints (optional)Same as youre used to

• Reject any poses that does not have at least one
  atom in each constraint
• Each constraint may have associated SMARTS
  patters
• Only atoms matching the SMARTS pattern can
  satisfy the constraint
• If no SMARTS pattern is specified any atom can
  satisfy the constraint
• The user specifies the constraints with -pharm

constraint
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Scoring

• Available functions
• -cgauss ChemGauss
• -plp PLP
• -shapegauss GSF
• No optimization
• Tens of thousands of poses are scored

How many poses are retained
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Rescoring

• Available functions
• -chemscore
• -zap_bind
• MMFF Optimization with Zap Bind
• Proton Optimization with Chemscore
• Operate on best poses from Scoring

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MASC

• Requires special prep of ligand database
• Program masc_prep distributed w/ FRED
• Same flags as FRED, except no active site
• Tags ligands with MASC data
• 5 potential tags for 5 scoring functions
• Created masc_ligands.oeb.gz file
• After prep
• Give masc_ligands.oeb.gz as dbase
• Specify masc flag