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Article ID: 1597 - Last Modified:

Why aren't the amine groups in aryl amines (e.g., aniline) coplanar with the aromatic ring, in my Glide poses?

Aniline nitrogens can be sp2-like or sp3-like depending on what is attached to them. For nitrogens attached to aryl groups, the nature of the aryl group itself (and its substituents) also affects whether planarity is favored. There is a competition between conjugation of the N lone pair with the ring and steric repulsion with the ortho substituents. The crystal structures in the CSD show a wide variety of geometries for aryl amines, as do ab initio calculations.

These subtleties make it difficult to develop a proper parameterization scheme for these kinds of amino groups. OPLS_2005 does favor planarity of the amino group, and coplanarity with the aromatic ring, but only weakly. Using the "Enhanced planarity of conjugated pi groups" option in the Ligand Docking panel increases the tendency toward both kinds of planarity, but in the Glide docking results this may not be enough to enforce planarity.

To force planarity in the Glide results, you can turn off post-docking minimization (on the Output tab), as this will preserve the original ligand bond geometries (i.e., only dihedrals will change). It's still possible that the planar nitrogen group could rotate out of the plane of the aryl; if so, a torsional constraint could be used to preserve the input aryl-N dihedral.

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