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Article ID: 775 - Last Modified:

How do I dock to a receptor like hERG without knowing if the drug is an activator or a blocker? hERG has a large inner cavity for receptor blocker ligands and pore domains and some external cavity activators.

You would have to generate grids centered at the blocker site and at each activator site, and then dock to each. Glide has been designed or validated for the purpose of comparing different ligands binding to a single site, not for comparing possible binding sites of a particular ligand, but the GlideScore and energy terms of the multiple docking runs should provide useful information.

Glide is likely to find poses for activators in the blocking site, if they are approximately the same size as the blockers. However,they should score poorly relative to the blockers, and relative to the activators docked to the activator sites.

Glide has been used with hERG in the context of the Induced Fit Docking workflow — see http://www.schrodinger.com/productpage/14/6/75/. Since this study involved docking to the blocker site in the pore, the grid was centered there.

Keywords: blocker site, activator site, hERG

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