Fig. 1.

Ring bending for elaboration of ring system flexibility: initial 3D structure generation produced a reasonable conformer for tetracycline (upper left); ring bends are identified among atoms of a ring system according to rules, with an example for cyclohexane shown (middle left); iterative application of the bends identifies new ring conformations effectively (bottom left). Ring twisting for macrocyclic search: the initial structure of cyclodecane (upper right) is shown with four atoms marked; those atoms seen through the 2–3 axis (middle right) are pushed through a twisting motion where atom 4 is forced around the axis; iterative application of this strategy results in an effective enumeration of ring conformers for cyclodecane