Flexible Ligand Docking with Glide

Matthew P. Repasky1, Mee Shelley1, Richard A. Friesner2

1 Schrodinger, L.L.C., Portland, Oregon, 2 Columbia University, New York, New York
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.12
DOI:  10.1002/0471250953.bi0812s18
Online Posting Date:  June, 2007
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Abstract

Glide is a ligand docking program for predicting protein‐ligand binding modes and ranking ligands via high‐throughput virtual screening. Glide utilizes two different scoring functions, SP and XP GlideScore, to rank‐order compounds. Three modes of sampling ligand conformational and positional degrees of freedom are available to determine the optimal ligand orientation relative to a rigid protein receptor geometry. This unit presents protocols for flexible ligand docking with Glide, optionally including ligand constraints or ligand molecular similarities.

Keywords: ligand docking; protein‐ligand interactions; protein‐ligand binding

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Grid Generation
  • Basic Protocol 2: Flexible Ligand Docking
  • Alternate Protocol 1: Grid Generation with Constraints
  • Alternate Protocol 2: Flexible Ligand Docking with Constraints
  • Alternate Protocol 3: Flexible Ligand Docking with Similarity
  • Support Protocol 1: Ligand Preparation
  • Support Protocol 2: Receptor Preparation
  • Support Protocol 3: Software Installation
  • Guidelines for Understanding Results
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

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Figures

Videos

Literature Cited

   Friesner, R.A., Banks, J.L., Murphy, R.B., Halgren, T.A., Klicic, J.J., Mainz, D.T., Repasky, M.P., Knoll, E.H., Shelley, M., Perry, J.K., Shaw, D.E., Francis, P., and Shenkin, P.S. 2004. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47:1739‐1749.
   Friesner, R.A., Murphy, R.B., Repasky, M.P., Frye, L.L., Greenwood, J.R., Halgren, T.A., Sanschagrin, P.C., and Mainz, D.T. 2006. Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein‐ligand complexes. J. Med. Chem. 49:6177‐6196.
   Halgren, T.A., Murphy, R.B., Friesner, R.A., Beard, H.S., Frye, L.L., Pollard, W.T., and Banks, J.L. 2004. Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47:1750‐1759.
   Kontoyianni, M., McClellan, L.M., and Sokol, G.S. 2004. Evaluation of docking performance: Comparative data on docking algorithms. J. Med. Chem. 47:558‐565.
   Krovat, E.M., Steindl, T., and Langer, T. 2005. Recent advances in docking and scoring. Curr. Comp. Aid Drug Des. 1:93‐102.
   Pearlman, D.A. and Charifson, P.S. 2001. Improved scoring of ligand‐protein interactions using OWFEG free energy grids. J. Med. Chem. 44:502‐511.
   Perola, E., Walters, W.P., and Charifson, P.S. 2004. A detailed comparison of current docking and scoring methods on systems of pharmaceutical relevance. Proteins 56:235‐249.
   Sherman, W., Day, T., Jacobson, M.P., Friesner, R.A., and Farid, R. 2006. Novel procedure for modeling ligand/receptor induced fit effects. J. Med. Chem. 49:534‐553.
   Teague, S.J. 1996. Implications of protein flexibility for drug discovery. Nature Rev. Drug Discovery 9:175‐186.
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