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Standard parameters of FlexX 1.13.2 program were used as implemented in SYBYL 6.9.2 package unless highlighted. The particle concept was always checked to simulate the significant role of structural water molecules in formation of protein-ligand complexes. Default protonation states were used as defined in FlexX. Formal charges at protein residues were normally assigned if not marked later. All stored poses were rescored using the CScore module of SYBYL 6.9.2 comprising the following functions: Dock, Chem, FlexX, PMF, and Gold scoring function. SYBYL 6.9.2 and FlexX 1.13.2 are available from Tripos Inc. 1699 South Hanley Road St. Louis, MO 63144-2319, USA.
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21944450075
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Definition of enrichment factor (EF): EF=fraction of active compounds in subset/fraction of active compounds in library.
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38
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39
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Ligand molecules were treated as neutral. 3D coordinates were generated from 2D coordinates using CONCORD 5.1.1 (Pearlman, R.S. Chem. Des. Auto. News, 1987, 2, 1) and at the same time the salts were dropped out. CONCORD transforms the information contained in a molecule's atomic connection table into atomic co-ordinates. One conformer was generated for each compound of the input library. Inactive molecules were chosen from WDI after applying 2D property filters, such as removal of compounds having molecular weight less than 200 or greater than 800, rotatable bonds more than 15, log P larger than 7. Molecules with metal atoms were also flagged. A set of well-known ERα ligands was mixed with inactive set to test the robustness of the process.
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