Knowledge Base

Article ID: 214 - Last Modified:

Can I create a pharmacophore hypothesis based only on my protein binding site, without having a native ligand?

You can do this with the script E-Pharmacophores. This script is included in the software distribution (Scripts → Docking Post-processing → E-Pharmacophores).

You will need some structures in the binding site on which to base the pharmacophore model. For this purpose, we recommend that you dock fragment molecules to your binding site with Glide XP and ensure that you select "Write XP descriptor information." (Note that you need an XP Visualizer license in addition to a Glide license to run this job.) For example, you could use the fragment molecules provided on our website:

The E-Pharmacophores script creates a Phase hypothesis from docked poses based on the Glide XP descriptor energies associated with each pharmacophore feature. The pose viewer file from Glide is required as input. This file contains the XP descriptors. Because you will likely have many docked fragment poses from Glide, you should use the default option to cluster the fragments by volume overlap. Receptor-based excluded volumes can be optionally included.

The method is described in these two papers:

J. Chem. Inf. Model., 2009, 49 (10), 2356-2368
J. Comp. Aided Mol Des., 2009, 23 (8), 541-554

Keywords: receptor-based pharmacophore, e-pharmacophore

Related Articles:

#131: Is it possible to generate a structure-based pharmacophore model from the receptor binding site?

Back to Search Results

Was this information helpful?

What can we do to improve this information?

To ask a question or get help, please submit a support ticket or email us at
Knowledge Base Search

Type the words or phrases on which you would like to search, or click here to view a list of all
Knowledge Base articles