Glide Overview

These topics contain an overview of the Glide (Grid-based LIgand Docking with Energetics) program, its scientific methods and computational procedures.

Glide searches for favorable interactions between one or more ligand molecules and a 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 with rigid or flexible ligand conformations; the ligand conformations are generated automatically if flexible docking is requested. The combination of position and orientation of a ligand relative to the receptor, along with its conformation in flexible docking, 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 [1].

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 nonbonded ligand-receptor interaction energy.

Final scoring is then carried out on the energy-minimized poses. By default, Schrödinger’s proprietary GlideScore multi-ligand scoring function is used to score the poses. If GlideScore was selected as the scoring function, a composite Emodel score is then used to rank the poses of each ligand and to select the poses to 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.

Glide’s primary purpose is for screening large numbers of ligands bound by noncovalent interactions to a largely rigid receptor model. The Glide technology is used in conjunction with Prime technology to provide capabilities for covalently bound ligands and for flexible receptors. See the Covalent Docking User Manual — Contents and the Induced Fit Docking User Manual — Contents for information on these capabilities.

This section contains the following topics: