On the flexibility of β‐peptides

The full conformational space was explored for an achiral and two chiral β‐peptide models: namely For‐β‐Ala‐NH2, For‐β‐Abu‐NH2, and For‐β‐Aib‐NH2. Stability and conformational properties of all three model systems were computed at different levels of theory: RHF/3‐21G, B3LYP/6‐311++G(d,p)//RHF/3‐21G, B3LYP/6‐311++G(d,p), MP2//B3LYP/6‐311++G(d,p), CCSD//B3LYP/6‐311++G(d,p), and CCSD(T)//B3LYP/6‐311++G(d,p). In addition, ab initio E = E(φ, μ, ψ) potential energy hypersurfaces of all three models were determined, and their topologies were analyzed to determine the inherent flexibility properties of these β‐peptide models. Fewer points were found and assigned than expected on the basis of Multidimensional Conformational Analysis (MDCA). Furthermore, it has been demonstrated, that the four‐dimensional surface, E = E(φ, μ, ψ), can be reduced into a three‐dimensional one: E = E[φ, f(φ), ψ]. This reduction of dimensionality of freedom of motion suggests that β‐peptides are less flexible than one would have thought. This agrees with experimental data published on the conformational properties of peptides composed of β‐amino acid residues. © 2003 Wiley Periodicals, Inc. J Comput Chem 25: 285–307, 2004