The role of benzodiazepine derivatives (BZD) as a privileged scaffold that mimics beta-turn structures (Ripka et al. (1993) Tetrahedron 49:3593-3608) in peptide/protein recognition was reexamined in detail. Stable BZD ring conformers were determined with MM3, and experimental reverse-turn structures were extracted from the basis set of protein crystal structures previously defined by Ripka et al. Ideal beta-turns were also modeled and similarly compared with BZD conformers. Huge numbers of conformers were generated by systematically scanning the torsional degrees of freedom for BZDs, as well as those of ideal beta-turns for comparison. Using these structures, conformers of BZDs were fit to experimental structures as suggested by Ripka et al., or modeled classical beta-turn conformers, and the root-mean-square deviation (RMSD) values were calculated for each pairwise comparison. Pairs of conformers with the smallest RMSD values for overlap of the four alpha-beta side-chain orientations were selected. All overlaps of BZD conformers with experimental beta-turns yielded one or more comparisons where the least RMSD was significantly small, 0.48-0.86 angstroms, as previously suggested. Utilizing a different methodology, the overall conclusion that benzodiazepines could serve as reverse-turn mimetics of Ripka et al. is justified. The least RMSD values for the overlap of BZDs and modeled classical beta-turns were also less than 1 angstrom. When comparing BZDs with experimental or classical beta-turns, the set of experimental beta-turns selected by Ripka et al. fit the BZD scaffolds better than modeled classical beta-turns; however, all the experimental beta-turns did not fit a particular BZD scaffold better. A single BZD ring conformation, and/or chiral orientation, can mimic some, but not all, of the experimental beta-turn structures. BZD has two central ring conformations and one chiral center that explains why the four variations of the BZD scaffold can mimic all types of beta-turn structure examined. It was found, moreover, that the BZD scaffold also mimics each of the nine clusters of experimental orientations of side chains of reverse turns in the Protein Data Bank, when the new classification scheme for the four side-chain directions (the relative orientations of alpha-beta vectors of residues i through i+3) was considered (Tran et al. (2005) J Comput-Aided Mol Des 19:551-566).