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GRIDP: Web-enabled Drug Discovery

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 it’s not like I have a drug-company budget…. GOAL: Screen 100 find a hit.

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GRIDP: Web-enabled Drug Discovery

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  1. 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 it’s not like I have a drug-company budget…

  2. GOAL: Screen 100 find a hit.

  3. Starting Point

  4. Active Molecule

  5. Active Molecule

  6. Protein Structure (Homology)

  7. Refine, Dock, Simulate • Refine, Simulate (shared memory) • 10K’s to 100K’s 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

  8. Problem for Biologists/Chemists

  9. 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_data : 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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