Conformation of cyclic dipeptides from empirical energy calculations

Empirical energy calculations on cyclo-Gly-X with X- Phe, Tyr, Val, and Leu as a function of the side-chain torsion angles χ indicate that the conformation of minimum energy are characterized by χ₁ = 60°, χ² = 90° for Phe and Try, χ¹ = ?60° for Val and χ¹ = ?60°, χ² = 180° and χ¹ = 60° and χ² = 150° for Leu. The minimum energy conformation of cyclo-Gly-Phe and cyclo-Gly-Val have the side chains of Phe and Val stacked over the poperazinedione ring as suggested by NMR and found for cyclo-Gly-Tyr crystal structure. In contrast, the Leu side chain is expected to exist in an extended or a quasi-folded form.