Glide Overview
- Using
- Additional Resources
Summary
Glide (Grid-based LIgand Docking with Energetics) searches for favorable interactions between one or more typically small ligand molecules and a typically larger receptor molecule, usually a protein. Each ligand must be a single molecule, while the receptor may include more than one molecule, e.g., a protein and a cofactor. Glide can be run in rigid or flexible docking modes; the latter automatically generates conformations for each input ligand. The combination of a ligand conformation (for rigid docking, the input conformation; for flexible docking, a generated conformation) with its position and orientation is referred to as a ligand pose.
The ligand poses that Glide generates pass through a series of hierarchical filters that evaluate the ligand's interaction with the receptor. The initial filters test the spatial fit of the ligand to the defined active site, and examine the complementarity of ligand-receptor interactions using a grid-based method patterned after the empirical ChemScore function (Eldridge et al., J.Comput. Aided Mol. Des.1997, 11, 425-445).
Poses that pass these initial screens enter the final stage of the algorithm, which involves evaluation and minimization of a grid approximation to the OPLS-AA nonbonded ligand-receptor interaction energy.
Final scoring, which by default uses Schrödinger's proprietary GlideScore multi-ligand scoring function, is then carried out on the energy-minimized poses. Finally, if GlideScore was selected as the scoring function, a composite Emodel score is used to rank the ligand poses and to select which pose (or poses, if so specified) for a given ligand will be reported to the user. Emodel combines GlideScore, the nonbonded interaction energy, and, for flexible docking, the excess internal energy of the generated ligand conformation.
Using Glide
The Glide task most frequently performed is ligand docking. The grid files produced by a single receptor grid generation task can be used for any number of jobs docking ligands to that receptor. Before generating receptor grids, it is strongly recommended that you prepare the protein. Therefore, the first steps of a typical project beginning with an unprepared protein-ligand complex structure (e.g., from PDB) might proceed using the Glide panels as follows:
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Prepare the protein using the Protein Preparation Workflow Panel. In this process, you should check the correctness of formal charges and bond orders in the ligand, cofactors, and nonstandard residues.
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With the prepared receptor-ligand complex in the Workspace, use the Receptor Grid Generation Panel to specify settings, optionally define Glide constraints, and start the receptor grid generation job.
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Prepare the ligands using LigPrep, to ensure that the structures are all-atom, minimized 3D structures.
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Specify the base name for the receptor grid files you want to use in the Ligand Docking Panel, and use the other settings and options in the panel to set up and start a ligand docking job. As many docking jobs as you want can be set up in this panel, using the current receptor grids or specifying a different set of grids to use.