Conformational behavior of α,α‐dialkylated peptides: Ab initio and empirical results for cyclopropylglycine

Abstract

Abstract The preferred conformations of model cyclopropylglycine peptides have been investigated by means of ab initio and empirical methods. Empirical computations performed with fixed bond lengths and valence angles using two well‐known force fields show that only values of ϕ in the ranges ±70° ± 20° are sterically allowed, and that the C 7 ‐conformation corresponds to the absolute energy minimum irrespective of the terminal groups used. Also, ab initio computations give similar results, but suggest greater stabilities for bridge and, especially, extended structures. These discrepancies can be removed, adding to the empirical force field a twofold torsional potential on ψ and using softer steric repulsive potentials. Complete geometry optimization using both ab initio and empirical methods does not affect the relative stabilities of folded conformations, but leads to a further significant stabilization of the fully extended structure via large modifications of some valence angles.