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Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening | Journal of Medicinal Chemistry

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ADVERTISEMENT Journal of Medicinal ChemistryVol 47/Issue 7Article Cite Share Jump to Expand ARTICLEFebruary 27, 2004 Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening Thomas A. HalgrenRobert B. MurphyRichard A. FriesnerHege S. BeardLeah L. FryeW. Thomas PollardJay L. Banks View Author Information View Author Information Loading Institutional Login Options… Other Access Options Supporting Information (1) Abstract

Glide's 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 “druglike” 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 1.8, 2.0, and 2.5 of Glide. The comparisons show that average measures for both “early” and “global” enrichment for Glide 2.5 are 3 times higher than for Glide 1.8 and more than 2 times higher than for Glide 2.0 because of better results for the least well-handled screens. This improvement in enrichment stems largely from the better balance of the more widely parametrized GlideScore 2.5 function and the inclusion of terms that penalize ligand−protein 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 co-workers (J. Med. Chem. 2000, 43, 4759−4767) show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01.

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To whom correspondence should be addressed. Phone: 646-366-9555, extension 106. Fax: 646-366-9550. E-mail: halgren@ schrodinger.com.

†

Schrödinger, L.L.C., NY.

‡

Columbia University.

Schrödinger, L.L.C., OR.

Supporting Information Available

Tables S1−S15, listing ranks of the active ligands, their GlideScore values, their hydrogen-bonding scores, and their Coluomb−vdW interaction energies with the protein site for the 15 database screens considered in this paper. This material is available free of charge via the Internet at http://pubs.acs.org.

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Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening

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Chem. 2004, 47, 7, 1750–1759 https://doi.org/10.1021/jm030644s Published February 27, 2004 Copyright © 2004 American Chemical Society Request reuse permissions Article Views 16k Citations 4453 Learn about these metrics Recommended Articles Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein−Ligand Complexes September 23, 2006Journal of Medicinal Chemistry Richard A. Friesner, Robert B. Murphy, Matthew P. Repasky, Leah L. Frye, Jeremy R. Greenwood, Thomas A. Halgren, Paul C. Sanschagrin, and Daniel T. Mainz OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space June 7, 2021Journal of Chemical Theory and Computation Chao Lu, Chuanjie Wu, Delaram Ghoreishi, Wei Chen, Lingle Wang, Wolfgang Damm, Gregory A. Ross, Markus K. Dahlgren, Ellery Russell, Christopher D. Von Bargen, Robert Abel, Richard A. Friesner, and Edward D. Harder* Show more recommended articles