How does Glide treat amide bond rotations?

You can choose one of four options for the treatment of amide bonds: Penalize non-planar conformation (the default), Retain original conformation, Vary conformation, or Allow trans conformation only. The first three options are available for all docking precisions (HTVS, SP, and XP); the last is not available for HTVS docking.

With the penalize option, an energy penalty is applied to twisted and cis conformations. Cis conformations are not penalized as much as twisted amides. The cis penalty is not applied to ureas and related amides, because the actual cis/trans ratio depends on the substituents. The cis-trans rotation barrier is approximately 6 kcal/mol when penalties are applied, so it is always possible to get poses with twisted amides if there are compensating interactions. Allowing some amide distortion, like allowing close intra-ligand contacts, is a means Glide uses to account for the lack of receptor flexibility.

Keywords: Glide, amide bonds, penalties, cis, trans

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