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How do I know whether to flip or rotate Ring-NHR, Ring-NR1R2 and protonated carboxylic acids when setting ligand flexibility?

Solution

When setting ligand flexibility, by default, all planar Ring-NHR, Ring-NR1R2 and carboxylic acids are set to 'Flip' i.e. to rotate through 180 degrees only.

For Ring-NHR and Ring-NR1R2, the Ring in each case is an aromatic ring but the R, R1 and/or R2 rings are not necessarily aromatic. If R, R1 and/or R2 are aromatic, then flipping should be used - this is because conjugation favours a planar conformation. If R, R1 and/or R2 are not aromatic, then free rotation should instead be used - this is for hindered systems where steric crowding will prevent the planar conformation from occurring.