A complete solution for ligand-receptor docking

The Advantages of Computational Docking

The widespread use of combinatorial chemistry and high-throughput screening (HTS) in the pharmaceutical and biotechnology industries means that large numbers of compounds can now routinely be investigated for biological activity. However, screening large chemical libraries remains an expensive and time-consuming process, with significant rates of both false positives and false negatives.

High-speed computational methods can now enrich the fraction of suitable lead candidates in a chemical database, thereby creating the potential to greatly enhance productivity and dramatically reduce drug development costs. With an ever increasing number of drug discovery projects having access to high-resolution crystal structures of their targets, high-performance ligand-receptor docking is the clear computational strategy of choice to augment and accelerate structure-based drug design.

Complete solution:
Glide offers the full range of speed vs. accuracy options, from the HTVS (high-throughput virtual screening) mode for efficiently enriching million compound libraries, to the SP (standard precision) mode for reliably docking tens to hundreds of thousands of ligand with high accuracy, to the XP (extra precision) mode where further elimination of false positives is accomplished by more extensive sampling and advanced scoring, resulting in even higher enrichment.

Virtual screening:
Glide provides a rational workflow for virtual screening from HTVS to SP to XP, enriching the data at every level such that only an order of magnitude fewer compounds need to be studied at the next higher accuracy level.

Accurate binding mode prediction:
Glide reliably finds the correct binding modes for a large set of test cases. It outperforms other docking programs in achieving lower RMS deviations from native co-crystallized structures.

Universal applicability:
Glide exhibits excellent docking accuracy and high enrichment across a diverse range of receptor types.

Fully prepared databases of purchasable compounds from Enamine, MolPort, MilliporeSigma, and Mcule:
Schrödinger has partnered with Enamine, MilliporeSigma, MolPort and Mcule to provide a Phase database of fragments, lead-like, near drug-like, and drug-like compounds available from Enamine's "Stock Screening Compounds Collection", MilliporeSigma's "Aldrich Market Select", MolPort's "Screening Compound Database", and Mcule's Mcule In Stock Purchasable database, respectively.

Citations and Acknowledgements

Schrödinger Release 2021-4: Glide, Schrödinger, LLC, New York, NY, 2021.

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ö Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L., "Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening," J. Med. Chem., 2004, 47, 1750–1759

ö Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shaw, D. E.; Shelley, M.; Perry, J. K.; Francis, P.; Shenkin, P. S., "Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy," J. Med. Chem., 2004, 47, 1739–1749

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"Validation of Molecular Docking Calculations Involving FGF-1 and FGF-2"

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"Application of Machine Learning To Improve the Results of High-Throughput Docking Against the HIV-1 Protease"

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"A Detailed Comparison of Current Docking and Scoring Methods on Systems of Pharmaceutical Relevance"

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"Development and Characterization of Nonpeptidic Small Molecule Inhibitors of the XIAP/Caspase-3 Interaction"

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"Synthesis of Novel Thrombin Inhibitors. Use of Ring-Closing Metathesis Reactions for Synthesis of P2 Cyclopentene- and Cyclohexenedicarboxylic Acid Derivatives"

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Johansen, T. N.; Greenwood, J. R.; Frydenvang, K.; Madsen, U.; Krogsgaard-Larsen, P., Chirality, 2003, 15, 167–179

"Synthesis and Discovery of Macrocyclic Polyoxygenated Bis-7-azaindolylmaleimides as a Novel Series of Potent and Highly Selective Glycogen Synthase Kinase-3 Inhibitors"

Kuo, G.-H.; Prouty, C.; DeAngelis, A.; Shen, L.; O'Neill, D. J.; Shah, C.; Connolly, P. J.; Murray, W. V.; Conway, B. R.; Cheung, P.; Westover, L.; Xu, J. Z.; Look, R. A.; Demarest, K. T.; Emanuel, S.; Middleton, S. A.; Jolliffe, L.; Beavers, M. P.; Chen,, J. Med. Chem., 2003, 46, 4021–4031

"Rational Design, Synthesis, and Pharmacological Evaluation of 2-Azanorbornane-3-exo,5-endo-dicarboxylic Acid: A Novel Conformationally Restricted Glutamic Acid Analogue"

Bunch, L.; Liljefors, T.; Greenwood, J. R.; Frydenvang, K.; Brauner-Osborne, H.; Krogsgaard-Larsen, P.; Madsen, U., J. Org. Chem., 2003, 68, 1489–1495

"Selective Agonists at Group II Metabotropic Glutamate Receptors: Synthesis, Stereochemistry, and Molecular Pharmacology of (S)- and (R)-2-Amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl) butyric Acid"

lausen, R. P.; Brauner-Osborne, H.; Greenwood, J. R.; Hermit, M. B.; Stensbol, T. B.; Nielsen, B.; Krogsgaard-Larsen, P., J. Med. Chem., 2002, 45, 4240–4245

"Metal-Dependent Inhibition of HIV-1 Integrase"

Neamati, N.; Lin, Z.; Karki, R. G.; Orr, A.; Cowansage, K.; Strumberg, D.; Pais, G. C. G.; Voigt, J. H.; Nicklaus, M. C.; Winslow, H. E.; Zhao, H.; Turpin, J. A.; Yi, J.; Skalka, A. M.; Burke, T. R., Jr.; Pommier, Y., J. Med. Chem., 2002, 45, 5661–5670

"Solvent Models for Protein-Ligand Binding: Comparison of Implicit Solvent Poisson and Surface Generalized Born Models with Explicit Solvent Simulations"

Zhang, L.Y.; Gallicchio, E.; Friesner, R.A.; Levy, R.M., J. Comput. Chem., 2001, 22, 591–607

Drug-Like Ligand Decoys Set

Schrödinger has made available a set of the ligand decoys used in Glide enrichment studies.

1K Drug-Like Ligand Decoys Set: This collection of ligands was created by selecting 1000 ligands from a one million compound library that were chosen to exhibit "drug-like" properties. Creation and application of the ligand set is presented in the following publications:

Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shaw, D. E.; Shelley, M.; Perry, J. K.; Francis, P.; Shenkin, P. S, "Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy", J. Med. Chem. 2004, 47, 1739-1749.

Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L., "Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening", J. Med. Chem. 2004, 47, 1750-1759.


Last updated 11/17/2009


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