John J Irwin

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking
    Michael M Mysinger
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158 2330, USA
    J Med Chem 55:6582-94. 2012
  2. pmc ZINC: a free tool to discover chemistry for biology
    John J Irwin
    Department of Pharmaceutical Chemistry, Byers Hall, University of California San Francisco, 1700 fourth St, Box 2550, San Francisco, California 94158 2330, United States
    J Chem Inf Model 52:1757-68. 2012
  3. doi request reprint Community benchmarks for virtual screening
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, PO Box 2550, Byers Hall, San Francisco, CA 94158 2330, USA
    J Comput Aided Mol Des 22:193-9. 2008
  4. pmc Automated docking screens: a feasibility study
    John J Irwin
    Department of Pharmaceutical Chemistry, Byers Hall, Box 2550, University of California San Francisco, San Francisco, California 94158 2330, USA
    J Med Chem 52:5712-20. 2009
  5. ncbi request reprint How good is your screening library?
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco, CA 94143 2550, USA
    Curr Opin Chem Biol 10:352-6. 2006
  6. pmc Ligand discovery from a dopamine D3 receptor homology model and crystal structure
    Jens Carlsson
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA
    Nat Chem Biol 7:769-78. 2011
  7. pmc Identifying mechanism-of-action targets for drugs and probes
    Elisabet Gregori-Puigjané
    Department of Pharmaceutical Chemistry, University of California, 1700 Fourth Street, San Francisco, CA 94143 2550, USA
    Proc Natl Acad Sci U S A 109:11178-83. 2012
  8. pmc Statistical potential for modeling and ranking of protein-ligand interactions
    Hao Fan
    Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA
    J Chem Inf Model 51:3078-92. 2011
  9. ncbi request reprint Relating protein pharmacology by ligand chemistry
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
    Nat Biotechnol 25:197-206. 2007
  10. pmc Benchmarking sets for molecular docking
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
    J Med Chem 49:6789-801. 2006

Collaborators

Detail Information

Publications38

  1. pmc Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking
    Michael M Mysinger
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158 2330, USA
    J Med Chem 55:6582-94. 2012
    ..We test this data set by docking all 102 targets, using the results to improve the balance between ligand desolvation and electrostatics in DOCK 3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org...
  2. pmc ZINC: a free tool to discover chemistry for biology
    John J Irwin
    Department of Pharmaceutical Chemistry, Byers Hall, University of California San Francisco, 1700 fourth St, Box 2550, San Francisco, California 94158 2330, United States
    J Chem Inf Model 52:1757-68. 2012
    ..Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org...
  3. doi request reprint Community benchmarks for virtual screening
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, PO Box 2550, Byers Hall, San Francisco, CA 94158 2330, USA
    J Comput Aided Mol Des 22:193-9. 2008
    ..Careful attention to both the composition of benchmarks and how they are used is essential to avoid being misled by overfitting and bias...
  4. pmc Automated docking screens: a feasibility study
    John J Irwin
    Department of Pharmaceutical Chemistry, Byers Hall, Box 2550, University of California San Francisco, San Francisco, California 94158 2330, USA
    J Med Chem 52:5712-20. 2009
    ..DOCK Blaster is available at http://blaster.docking.org ...
  5. ncbi request reprint How good is your screening library?
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco, CA 94143 2550, USA
    Curr Opin Chem Biol 10:352-6. 2006
    ..The best general-purpose screening libraries may well be those of intermediate complexity that are free of artifact-causing nuisance compounds...
  6. pmc Ligand discovery from a dopamine D3 receptor homology model and crystal structure
    Jens Carlsson
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA
    Nat Chem Biol 7:769-78. 2011
    ..3 to 3.0 μM. One of the new ligands from the homology model screen was optimized for affinity to 81 nM. The feasibility of docking screens against modeled GPCRs more generally is considered...
  7. pmc Identifying mechanism-of-action targets for drugs and probes
    Elisabet Gregori-Puigjané
    Department of Pharmaceutical Chemistry, University of California, 1700 Fourth Street, San Francisco, CA 94143 2550, USA
    Proc Natl Acad Sci U S A 109:11178-83. 2012
    ..A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest...
  8. pmc Statistical potential for modeling and ranking of protein-ligand interactions
    Hao Fan
    Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, USA
    J Chem Inf Model 51:3078-92. 2011
    ..The statistical potentials are available through the Integrative Modeling Platform (IMP) software package (http://salilab.org/imp) and the LigScore Web server (http://salilab.org/ligscore/)...
  9. ncbi request reprint Relating protein pharmacology by ligand chemistry
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
    Nat Biotechnol 25:197-206. 2007
    ..These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves...
  10. pmc Benchmarking sets for molecular docking
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
    J Med Chem 49:6789-801. 2006
    ..DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/...
  11. pmc Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET
    Avner Schlessinger
    Department of Bioengineering and Therapeutic Sciences, and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 108:15810-5. 2011
    ..The observations highlight the utility of virtual screening against a comparative model, even when the target shares less than 30% sequence identity with its template structure and no known ligands in the primary binding site...
  12. ncbi request reprint Physics-based scoring of protein-ligand complexes: enrichment of known inhibitors in large-scale virtual screening
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, Genentech Hall, 94143 2240, USA
    J Chem Inf Model 46:243-53. 2006
    ..We also present anecdotal but encouraging results assessing the ability of the rescoring method to predict specificity of inhibitors for structurally related proteins...
  13. pmc Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors
    Rafaela S Ferreira
    Graduate Program in Chemistry and Chemical Biology, University of California San Francisco, California 94158, USA
    J Med Chem 53:4891-905. 2010
    ..Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone...
  14. pmc Predicting new molecular targets for known drugs
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, California 94143 2550, USA
    Nature 462:175-81. 2009
    ..The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs...
  15. pmc Ligand pose and orientational sampling in molecular docking
    Ryan G Coleman
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America
    PLoS ONE 8:e75992. 2013
    ..Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field...
  16. pmc Virtual ligand screening against comparative protein structure models
    Hao Fan
    Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, CA, USA
    Methods Mol Biol 819:105-26. 2012
    ..Here, we describe an integrated modeling and docking protocol, combining comparative modeling by MODELLER and virtual ligand screening by DOCK...
  17. ncbi request reprint Predicting substrates by docking high-energy intermediates to enzyme structures
    Johannes C Hermann
    Department of Pharmaceutical Chemistry, University of California, San Francisco, MC 2550, San Francisco, California 94158 2330, USA
    J Am Chem Soc 128:15882-91. 2006
    ..The possible applications of this approach to other enzymes are considered...
  18. pmc Quantifying biogenic bias in screening libraries
    Jérôme Hert
    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA
    Nat Chem Biol 5:479-83. 2009
    ..We have developed a method to quantify the bias in screening libraries toward biogenic molecules. With this approach, we consider what is missing from screening libraries and how they can be optimized...
  19. pmc The chemical basis of pharmacology
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158 2558, USA
    Biochemistry 49:10267-76. 2010
    ..The bases for these new methods, some of their successes and liabilities, and new opportunities for their use are described...
  20. pmc Docking screens: right for the right reasons?
    Peter Kolb
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158 2330, USA
    Curr Top Med Chem 9:755-70. 2009
    ..We hope this review will motivate investigators to solve structures and compare them with their predictions whenever possible, to advance the field...
  21. pmc Structure-based ligand discovery for the Large-neutral Amino Acid Transporter 1, LAT-1
    Ethan G Geier
    Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 110:5480-5. 2013
    ..Finally, two of our hits inhibited proliferation of a cancer cell line by distinct mechanisms, providing useful chemical tools to characterize the role of LAT-1 in cancer metabolism...
  22. pmc Novel compounds lowering the cellular isoform of the human prion protein in cultured human cells
    B Michael Silber
    Institute for Neurodegenerative Diseases, University of California, San Francisco, United States Department of Neurology, University of California, San Francisco, United States Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States
    Bioorg Med Chem 22:1960-72. 2014
    ..Conclusions: Our studies identified leads for future studies to determine which compounds might lower PrP(C) levels in rodent brain, and provide the basis of a therapeutic for fatal disorders caused by PrP prions. ..
  23. pmc Chemical informatics and target identification in a zebrafish phenotypic screen
    Christian Laggner
    Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA
    Nat Chem Biol 8:144-6. 2012
    ..The roles of two of these targets were tested in the original zebrafish phenotype. Prediction of targets from chemotype is rapid and may be generally applicable...
  24. pmc Molecular docking screens using comparative models of proteins
    Hao Fan
    Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, San Francisco, California 94158, USA
    J Chem Inf Model 49:2512-27. 2009
    ..Even for single models, the models are significantly more enriching than the template structure if the template is paralogous and shares more than 25% sequence identity with the target...
  25. pmc Structure-based discovery of A2A adenosine receptor ligands
    Jens Carlsson
    Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, Box 2550, San Francisco, California 94158, USA
    J Med Chem 53:3748-55. 2010
    ..Despite this bias, many of the most potent new ligands were novel, dissimilar from known ligands, providing new lead structures for modulation of this medically important target...
  26. pmc Docking and chemoinformatic screens for new ligands and targets
    Peter Kolb
    Dept of Pharmaceutical Chemistry, University of California, San Francisco, 1700 4th St, Byers Hall Room 508D, San Francisco, CA 94158 2550, United States
    Curr Opin Biotechnol 20:429-36. 2009
    ....
  27. pmc Quantifying the relationships among drug classes
    Jérôme Hert
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco, California 94143 2550, USA
    J Chem Inf Model 48:755-65. 2008
    ..Also, the chemoinformatics networks were more natural and more organized, by network theory, than their bioinformatics counterparts: ligand-based networks were found to be small-world and broad-scale...
  28. pmc Structure-based discovery of beta2-adrenergic receptor ligands
    Peter Kolb
    Department of Pharmaceutical Chemistry, University of California, 1700 4th Street, Box 2550, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 106:6843-8. 2009
    ....
  29. ncbi request reprint Virtual screening against metalloenzymes for inhibitors and substrates
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California, San Francisco 94143 2550, USA
    Biochemistry 44:12316-28. 2005
    ..These results suggest that a simple, noncovalent scoring function may be used to identify inhibitors of at least some metalloenzymes...
  30. pmc Structure-based discovery of antagonists of nuclear receptor LRH-1
    Cindy Benod
    Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA
    J Biol Chem 288:19830-44. 2013
    ..Our data suggest that specific antagonists of LRH-1 could be used as specific molecular probes for elucidating the roles of the receptor in different types of malignancies. ..
  31. pmc Here be dragons: docking and screening in an uncharted region of chemical space
    Ruth Brenk
    University of California, San Francisco, Department of Pharmaceutical Chemistry, 1700 4th Street, San Francisco, CA 94143 2550, USA
    J Biomol Screen 10:667-74. 2005
    ..Subsequent retesting of high-scoring docked molecules may have found 2 true inhibitors, although this remains uncertain due to experimental ambiguities. The implications of this study for screening campaigns are considered...
  32. pmc Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase
    Kerim Babaoglu
    Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158 2330, USA
    J Med Chem 51:2502-11. 2008
    ..Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens...
  33. ncbi request reprint Using ZINC to acquire a virtual screening library
    John J Irwin
    University of California San Francisco, San Francisco, California, USA
    Curr Protoc Bioinformatics . 2008
    ..ZINC has a search facility, as well as a service to process molecules that are not in ZINC by uploading them to a server...
  34. pmc Antiprion compounds that reduce PrP(Sc) levels in dividing and stationary-phase cells
    B Michael Silber
    Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, United States Department of Neurology, University of California, San Francisco, CA 94143, United States Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, United States
    Bioorg Med Chem 21:7999-8012. 2013
    ..5 and 1.6 μM, respectively. Unexpectedly, the number of hits in stationary-phase cells was ~10% of that in dividing cells. The explanation for this difference remains to be determined...
  35. pmc ZINC--a free database of commercially available compounds for virtual screening
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, Genentech Hall, 600 16th Street, San Francisco, California 94143, USA
    J Chem Inf Model 45:177-82. 2005
    ..Users can process their own molecules by uploading them to a server. Our hope is that this database will bring virtual screening libraries to a wide community of structural biologists and medicinal chemists...
  36. ncbi request reprint Chemistry in cancer research: a vital partnership
    Shana J Sturla
    Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA
    ACS Chem Biol 2:286-92. 2007
  37. ncbi request reprint Chemistry in cancer research: a vital partnership
    Shana J Sturla
    Department of Medicinal Chemistry and The Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
    Cancer Res 67:6539-43. 2007
  38. ncbi request reprint Lead discovery using molecular docking
    Brian K Shoichet
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611 3008, USA
    Curr Opin Chem Biol 6:439-46. 2002
    ..With more docking studies being undertaken, the 'drug-likeness' and specificity of docking hits is also being examined...