Solubility and Membrane Permeability of Cyclic Dipeptides Approximately Estimated by Quantum Chemistry and Molecular Dynamics Calculations

Using both quantum chemical and molecular dynamics calculations, free energy profiles during membrane permeable processes of Ala-containing cyclic dipeptides were evaluated with moderate computational costs. Since the balance between hydrophobicity and hydrophilicity is a key factor in the membrane permeation processes, Ala-Ala and Ala-Pro might be permeable, but Ala-Asn is not owing to the high free energy barrier at the membrane center. This protocol is useful to roughly distinguish whether a given compound has high permeability or not.