R P Sheridan

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint Designing targeted libraries with genetic algorithms
    R P Sheridan
    Department of Molecular Systems, Merck Research Laboratories, P O B 2000, Rahway, NJ 07065, USA
    J Mol Graph Model 18:320-34, 525. 2000
  2. doi request reprint Time-split cross-validation as a method for estimating the goodness of prospective prediction
    Robert P Sheridan
    Cheminformatics Department, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 53:783-90. 2013
  3. doi request reprint Chemical similarity searches: when is complexity justified?
    Robert P Sheridan
    RY50S 100, Merck Research Laboratories, Rahway, NJ 06065, USA
    Expert Opin Drug Discov 2:423-30. 2007
  4. doi request reprint Three useful dimensions for domain applicability in QSAR models using random forest
    Robert P Sheridan
    Chemistry Modeling and Informatics, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 52:814-23. 2012
  5. ncbi request reprint Calculating similarities between biological activities in the MDL Drug Data Report database
    Robert P Sheridan
    RY50S 100 Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Comput Sci 44:727-40. 2004
  6. ncbi request reprint Empirical regioselectivity models for human cytochromes P450 3A4, 2D6, and 2C9
    Robert P Sheridan
    Molecular Systems Department, RY50S 100, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Med Chem 50:3173-84. 2007
  7. doi request reprint Alternative global goodness metrics and sensitivity analysis: heuristics to check the robustness of conclusions from studies comparing virtual screening methods
    Robert P Sheridan
    Molecular Systems, Merck Research Laboratories, RY50SW 100, Rahway, New Jersey 07065, USA
    J Chem Inf Model 48:426-33. 2008
  8. doi request reprint Multiple protein structures and multiple ligands: effects on the apparent goodness of virtual screening results
    Robert P Sheridan
    Molecular Systems Department, Merck Research Laboratories, RY50SW 100, Rahway, NJ 07065, USA
    J Comput Aided Mol Des 22:257-65. 2008
  9. doi request reprint QSAR models for predicting the similarity in binding profiles for pairs of protein kinases and the variation of models between experimental data sets
    Robert P Sheridan
    Chemistry Modeling and Informatics Department, Merck Research Laboratories, RY50SW 100, Rahway, NJ 07065, USA
    J Chem Inf Model 49:1974-85. 2009
  10. doi request reprint Drug-like density: a method of quantifying the "bindability" of a protein target based on a very large set of pockets and drug-like ligands from the Protein Data Bank
    Robert P Sheridan
    Chemistry Modeling and Informatics Department, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 50:2029-40. 2010

Detail Information

Publications29

  1. ncbi request reprint Designing targeted libraries with genetic algorithms
    R P Sheridan
    Department of Molecular Systems, Merck Research Laboratories, P O B 2000, Rahway, NJ 07065, USA
    J Mol Graph Model 18:320-34, 525. 2000
    ..2) We show that the approach of assembling libraries from fragments in high-scoring molecules is a reasonable one. (3) We compare results from a library-based GA to those from a molecule-based GA...
  2. doi request reprint Time-split cross-validation as a method for estimating the goodness of prospective prediction
    Robert P Sheridan
    Cheminformatics Department, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 53:783-90. 2013
    ..Time-split selection should be used in addition to random selection as a standard for cross-validation in QSAR model building...
  3. doi request reprint Chemical similarity searches: when is complexity justified?
    Robert P Sheridan
    RY50S 100, Merck Research Laboratories, Rahway, NJ 06065, USA
    Expert Opin Drug Discov 2:423-30. 2007
    ..One stated justification for adding complexity is that the methods are better able to 'lead-hop'. However, is this really true? I argue that only some types of complexity are useful in this regard...
  4. doi request reprint Three useful dimensions for domain applicability in QSAR models using random forest
    Robert P Sheridan
    Chemistry Modeling and Informatics, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 52:814-23. 2012
    ..We also show that the root-mean-square errors produced by cross-validation are predictive of root-mean-square errors of compounds tested after the model was built...
  5. ncbi request reprint Calculating similarities between biological activities in the MDL Drug Data Report database
    Robert P Sheridan
    RY50S 100 Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Comput Sci 44:727-40. 2004
    ..Two of these, TIMI and trend vector, show promise. Soft clustering of the activities using a union of similarity methods shows a reasonable association of therapeutic areas with their mechanisms...
  6. ncbi request reprint Empirical regioselectivity models for human cytochromes P450 3A4, 2D6, and 2C9
    Robert P Sheridan
    Molecular Systems Department, RY50S 100, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Med Chem 50:3173-84. 2007
    ..J. Med. Chem. 2003, 46, 1330-1336) and predictions from MetaSite (Cruciani et al. J. Med. Chem. 2005, 48, 6970-6979)...
  7. doi request reprint Alternative global goodness metrics and sensitivity analysis: heuristics to check the robustness of conclusions from studies comparing virtual screening methods
    Robert P Sheridan
    Molecular Systems, Merck Research Laboratories, RY50SW 100, Rahway, New Jersey 07065, USA
    J Chem Inf Model 48:426-33. 2008
    ..The major conclusions in that paper, for instance, that ligand-based methods are better than docking methods, hold up. However, some minor conclusions, such as Glide being the best docking method, do not...
  8. doi request reprint Multiple protein structures and multiple ligands: effects on the apparent goodness of virtual screening results
    Robert P Sheridan
    Molecular Systems Department, Merck Research Laboratories, RY50SW 100, Rahway, NJ 07065, USA
    J Comput Aided Mol Des 22:257-65. 2008
    ..2D similarity methods appear very good for the MDDR, but poor for the MCIDB. However, ROCS-color (a 3D similarity method) does well for both databases...
  9. doi request reprint QSAR models for predicting the similarity in binding profiles for pairs of protein kinases and the variation of models between experimental data sets
    Robert P Sheridan
    Chemistry Modeling and Informatics Department, Merck Research Laboratories, RY50SW 100, Rahway, NJ 07065, USA
    J Chem Inf Model 49:1974-85. 2009
    ..It is possible to build a model combining all the data from the five data sets that is reasonably self-consistent but not surprisingly, given the disagreement between data sets, less self-consistent than the individual models...
  10. doi request reprint Drug-like density: a method of quantifying the "bindability" of a protein target based on a very large set of pockets and drug-like ligands from the Protein Data Bank
    Robert P Sheridan
    Chemistry Modeling and Informatics Department, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Model 50:2029-40. 2010
    ..Nature Biotechnology 2007, 25, 71-75)...
  11. ncbi request reprint Finding multiactivity substructures by mining databases of drug-like compounds
    Robert P Sheridan
    RY50S 100, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Comput Sci 43:1037-50. 2003
    ..The method was applied to the USPDI and MDDR databases. There are clearly substructures in each database that occur in many compounds and span a variety of therapeutic categories. Some of these are expected, but some are not...
  12. ncbi request reprint Why do we need so many chemical similarity search methods?
    Robert P Sheridan
    Dept of Molecular Systems, RY50SW 100 Merck Research Laboratories, Rahway, NJ 07065, USA
    Drug Discov Today 7:903-11. 2002
    ..Also, any two methods tend to select different subsets of actives from a database, so it is advisable to use several search methods where possible...
  13. ncbi request reprint A simple method for visualizing the differences between related receptor sites
    Robert P Sheridan
    Department of Molecular Systems, RY50SW 100 Merck Research Laboratories, Rahway, NJ 07065, USA
    J Mol Graph Model 21:217-25. 2002
    ..We demonstrate the method on four examples: HIV proteases versus two-domain acid proteases, thrombin versus trypsin and factor Xa, bacterial dihydrofolate reductases (DHFRs) versus vertebrate DHFRs, and P38 versus ERK protein kinases...
  14. ncbi request reprint A simple method for visualizing the differences between related receptor sites
    Robert P Sheridan
    Department of Molecular Systems, Merck Research Laboratories, Rahway, NJ 07065, USA
    J Mol Graph Model 21:71-9. 2002
    ..We demonstrate the method on four examples: HIV proteases versus two-domain acid proteases, thrombin versus trypsin and factor Xa, bacterial dihydrofolate reductases (DHFRs) versus vertebrate DHFRs, and P38 versus ERK protein kinases...
  15. ncbi request reprint Protocols for bridging the peptide to nonpeptide gap in topological similarity searches
    R P Sheridan
    Department of Molecular Systems, RY50SW 100 Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    J Chem Inf Comput Sci 41:1395-406. 2001
    ..We demonstrate these protocols by using 10 peptide-like probes to select appropriate nonpeptide actives from the MDDR database...
  16. ncbi request reprint The most common chemical replacements in drug-like compounds
    Robert P Sheridan
    Department of Molecular Systems, RY50SW 100 Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Chem Inf Comput Sci 42:103-8. 2002
    ..This method can be applied to any set of molecules wherein the molecules can be paired by similar biological activity...
  17. ncbi request reprint Chemical similarity searches using latent semantic structural indexing (LaSSI) and comparison to TOPOSIM
    R D Hull
    Department of Molecular Systems, RY50S-100, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA
    J Med Chem 44:1185-91. 2001
    ..Typically, LaSSI selects very different sets of actives than does TOPOSIM, so it can find classes of actives that TOPOSIM would miss...
  18. ncbi request reprint Mining the chemical quarry with joint chemical probes: an application of latent semantic structure indexing (LaSSI) and TOPOSIM (Dice) to chemical database mining
    S B Singh
    Molecular Systems, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    J Med Chem 44:1564-75. 2001
    ..The use of multimolecule topological probes to identify compounds complements the use of searching databases with 3D pharmacophore hypotheses...
  19. ncbi request reprint Latent semantic structure indexing (LaSSI) for defining chemical similarity
    R D Hull
    Department of Molecular Systems, RY50S-100, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA
    J Med Chem 44:1177-84. 2001
    ..LaSSI also allows the calculation of the similarity between two descriptors and between a descriptor and a molecule...
  20. ncbi request reprint A model for predicting likely sites of CYP3A4-mediated metabolism on drug-like molecules
    Suresh B Singh
    Department of Molecular Systems Merck Research Laboratories, 126 E Lincoln Avenue, RY50SW 100, Rahway, New Jersey 07065 0900, USA
    J Med Chem 46:1330-6. 2003
    ..This model, in conjunction with specific enzyme site binding requirements, can aid in identifying possible sites of metabolism catalyzed by other cytochrome P450 enzymes...
  21. ncbi request reprint Mini review on molecular modeling of P-glycoprotein (Pgp)
    Sookhee N Ha
    Basic Chemistry, Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    Curr Top Med Chem 7:1525-9. 2007
    ..We review the recent developments from the point of view of methodology...
  22. ncbi request reprint Comparison of topological, shape, and docking methods in virtual screening
    Georgia B McGaughey
    Department of Molecular Systems, WP53F 301, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Chem Inf Model 47:1504-19. 2007
    ..Results for all virtual screening methods are database dependent and can vary greatly for particular targets...
  23. ncbi request reprint Amino acid substitution of arginine 80 in 17beta-hydroxysteroid dehydrogenase type 3 and its effect on NADPH cofactor binding and oxidation/reduction kinetics
    Brian M McKeever
    Merck Research Laboratories, Merck and Co, Inc, RY50 105, 126 East Lincoln Avenue, Rahway, NJ 07065, USA
    Biochim Biophys Acta 1601:29-37. 2002
    ..In no case was NADH found to substitute for NADPH...
  24. pmc Inhibition of recombinant cytochrome P450 isoforms 2D6 and 2C9 by diverse drug-like molecules
    Daniel R McMasters
    Department of Molecular Systems, Merck Research Laboratories, Rahway, New Jersey, USA
    J Med Chem 50:3205-13. 2007
    ..For CYP2C9, no clear trend between activity and physicochemical properties could be seen for the group as a whole; however, certain classes of compounds have altered frequencies of activity and atypical kinetics...
  25. ncbi request reprint Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors
    Ying Duo Gao
    Molecular Systems, Merck Research Laboratories, NJ, USA
    Bioorg Med Chem Lett 17:3877-9. 2007
    ..Compounds 3, 4, and 5 were synthesized and found to be potent DPP-4 inhibitors, in particular 4 and 5 are designed to be highly selective against off-target DASH enzymes while maintaining potency on DPP-4...
  26. ncbi request reprint Reagent Selector: using Synthon Analysis to visualize reagent properties and assist in combinatorial library design
    Ralph T Mosley
    Department of Molecular Systems, RY50SW 100, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    J Chem Inf Model 45:1439-46. 2005
    ..Ultimately, the reagent list that embodies the selected synthons is made available to the user for reagent procurement. Application of the approach to a sample reagent list for a G-protein coupled receptor targeted library is described...
  27. ncbi request reprint Web enabling technology for the design, enumeration, optimization and tracking of compound libraries
    Bradley P Feuston
    Molecular Systems Department, P O Box 4, West Point, PA 19486, USA
    Curr Top Med Chem 5:773-83. 2005
    ..In addition to accommodating project specific designs and virtual 3D library scanning, the application includes tools for parallel synthesis, laboratory automation and compound registration...
  28. ncbi request reprint Boosting: an ensemble learning tool for compound classification and QSAR modeling
    Vladimir Svetnik
    Biometrics Research and Molecular Systems, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    J Chem Inf Model 45:786-99. 2005
    ..The use of SGB's variable importance with partial dependence plots for model interpretation is also illustrated...
  29. ncbi request reprint Enhanced virtual screening by combined use of two docking methods: getting the most on a limited budget
    Vladimir Maiorov
    Molecular Systems, Merck Research Laboratories, Merck and Co, Inc, RY50SW 100, P O Box 2000, Rahway, New Jersey 07065, USA
    J Chem Inf Model 45:1017-23. 2005
    ..In more than half of the 20 cases examined, at least several actives per protein target were identified in approximately 24 hours per target...