Class Note for BINF 709 at KU
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This 2 page Class Notes was uploaded by an elite notetaker on Friday February 6, 2015. The Class Notes belongs to a course at Kansas taught by a professor in Fall. Since its upload, it has received 14 views.
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Date Created: 02/06/15
J Med Chem 2004 Mar 25477173949 Glide a new approach for rapid accurate docking and scoring 1 Method and assessment of docking accuracy Friesner RA Banks JL Murphy RB Halgren TA Klicic JJ Mainz DT Repasky m Knoll EH Shellev M Perrv JK Shaw DE Francis P Shenkin PS Department of Chemistry Columbia University New York New York 10036 USA richchemcolumbiaedu Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor Glide approximates a complete systematic search of the conformational orientational and positional space of the docked ligand In this search an initial rough positioning and scoring phase that dramatically narrows the search space is followed by torsionally flexible energy optimization on an OPLSAA nonbonded potential grid for a few hundred surviving candidate poses The very best candidates are further refined via a Monte Carlo sampling of pose conformation in some cases this is crucial to obtaining an accurate docked pose Selection of the best docked pose uses a model energy function that combines empirical and forcefieldbased terms Docking accuracy is assessed by redocking ligands from 282 cocrystallized PDB complexes starting from conformationally optimized ligand geometries that bear no memory of the correctly docked pose Errors in geometry for the topranked pose are less than 1 A in nearly half of the cases and are greater than 2 A in only about onethird of them Comparisons to published data on rms deviations show that Glide is nearly twice as accurate as GOLD and more than twice as accurate as FlexX for ligands having up to 20 rotatable bonds Glide is also found to be more accurate than the recently described Surflex method J Med Chem 2004 Mar 2547717509 Glide a new approach for rapid accurate docking and scoring 2 Enrichment factors in database screening Halgren TA Murphy RB Friesner RA Beard HS Frye LL Pollard WT Banks JL Schrodinger LLC 120 W 45th Street New York New York 10036 USA halgrenschrodingercom Glide39s ability to identify active compounds in a database screen is characterized by applying Glide to a diverse set of nine protein receptors In many cases two or even three protein sites are employed to probe the sensitivity of the results to the site geometry To make the database screens as realistic as possible the screens use sets of quotdruglikequot decoy ligands that have been selected to be representative of what we believe is likely to be found in the compound collection of a pharmaceutical or biotechnology company Results are presented for releases 18 20 and 25 of Glide The comparisons show that average measures for both quotearlyquot and quotglobalquot enrichment for Glide 25 are 3 times higherthan for Glide 18 and more than 2 times higher than for Glide 20 because of better results for the least wellhandled screens This improvement in enrichment stems largely from the better balance of the more widely parametrized GlideScore 25 function and the inclusion of terms that penalize ligandprotein interactions that violate established principles of physical chemistry particularly as it concerns the exposure to solvent of charged protein and ligand groups Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and coworkers J Med Chem 2000 43 47594767 show that Glide 25 performs better than GOLD 11 FlexX 18 or DOCK 401
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