GRIDP: Webenabled Drug Discovery

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GRIDP Web-enabled Drug Discovery

• Is there any way I can use computational tools to
  reduce the number of molecules I have to screen
  to a manageable number, like 100 or so, because
  even 100 is a stretch, and its not like I have a
  drug-company budget

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GOAL Screen 100 find a hit.
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Starting Point
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Active Molecule
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Active Molecule
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Protein Structure (Homology)
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Refine, Dock, Simulate

• Refine, Simulate (shared memory)
• 10Ks to 100Ks of atoms
• QM/MM calc, QM treatment of ligand and QM or MM
  treatment of protein for more accurate charges.
• Dock (parallel)
• Rigid 5 M candidates, up to 400 conformations
  each,
• 1060 potential drug-like molecules

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Problem for Biologists/Chemists
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Problem for Biologists/Chemists
Execute Options -param A parameter file
Inputting Ligands -dbase File of
multiconformer ligands. -conftest Set the
test for detecting if sequential molecule records
in the ligand database are
conformers. -molnames Tells FRED to only
dock molecules with names specified in a
text file -assign_ligand_charges
Assign AM1BCC charges to all input ligands.
MASC Preparation -reference_receptors
Text file listing custom masc reference
receptors files.
-no_masc_data_calc Don't calculate any
masc data for this run -recalculate_masc_da
ta Force re-calculation of masc data on
ligands with
existing data -report_masc_failures
Report failure of ligands to dock to masc
reference structures
Receptor Site -rec Receptor site file
molecules will be docked into. -pharm File
of custom docking constraints
-assign_protein_charges Assign MMFF charges to
receptor (otherwise
accept input) Create Site -pro
Protein molecule to convert into a receptor
site. -strip_water Strip waters from the
protein before creating the
receptor. -bound_ligand Known ligand
bound to the protein. -box A box
defining the receptor site -addbox
Adjusts the box created with the -box flag by
extending all sides by this
value -no_inner_contour Create the
receptor without an inner contour.
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