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Article ID: 739 - Last Modified: May 16, 2011

What are the advantages and disadvantages of Glide regular docking and induced fit docking?

Glide has been optimized for docking accuracy and database enrichment over a wide range of systems. In order to dock ligands in a reasonable time, the receptor is treated rigidly. This introduces some sensitivity to the particular receptor conformation used for docking. Glide softens the active site (via vdW scaling) in order to compensate for the lack of receptor flexibility. As long as there aren't significant receptor changes upon binding ligands, this generally is sufficient for screening applications.

If there are induced-fit effects upon binding ligands, however, using a single receptor conformation may penalize classes of actives that bind well to alternative conformations of the receptor. In such cases, it can be useful to perform ensemble docking (i.e., docking to mulitple receptor conformations, with optional GlideScore shifts to account for receptor reorganization energy). Our Virtual Screening Workflow can be used for this purpose.

It may be that no alternative receptor conformations are available, or perhaps only the apo form of a receptor is available. Our Induced Fit Docking workflow uses Glide and Prime to generate new receptor conformations and ligand binding modes. In brief, a ligand is docked with Glide to the original receptor structure, with many poses generated. Prime then is used to optimize the receptor structure with each particular ligand pose (the induced-fit part). The ligand is then redocked into the new receptor conformations, and the complexes are scored based both on the redocking GlideScore and the Prime energy from the optimization.

IFD is much more computationally intensive than Glide, and is not suitable for screening of large numbers of compounds, so you should always start with Glide; perhaps more complicated calculations won't be necessary in order to get good results.

Keywords: Glide docking, Induced Fit docking, IFD, VSW

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