LigPrep prepared my ring compounds in the equatorial conformation. However, after performing docking with Glide XP (with one pose per ligand), the compounds were in an axial conformation. Is there a reason for this?

LigPrep can generate multiple ring conformations, including both axial and equatorial conformations. It appears that the equatorial conformations are energetically more favorable.

The ring conformation generation in Glide is done via a template library that should generate both equatorial and axial forms, unless there is a significant energy difference between them. Glide's conformation generator also can generate multiple ring conformations, but it uses a narrower energy window than LigPrep in order to exclude cyclohexyl boat conformations. Therefore, it is likely that Glide is generating only the lower-energy equatorial conformations.

You could end up with only axial poses because
1) only axial conformations were generated, or
2) only the axial poses docked well.

If you want to retain the input ring conformations when running Glide docking, you can clear the 'Sample ring conformations' option on the Settings tab of the Ligand Docking panel. The rings then will remain in their input (equatorial) conformations throughout the docking process.

Keywords: ring conformation, axial, equatorial, LigPrep, Glide

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