Stacking Interactions of Heterocyclic Drug Fragments with Protein Amide Backbones

摘要: Stacking interactions can be important enthalpic contributors to drug binding. Among the less well-studied stacking are those occurring between an arene and π-face of amide group. Given ubiquity heterocycles in drugs, combined with abundance amides protein backbone, optimizing these noncovalent provide a potential route enhanced Previously, Diederich et al. (ChemMedChem 2013, 8, 397-404) studied stacked dimers model set 18 heterocycles, showing that computed interaction energies correlate dipole moments providing guidelines for optimization interactions. We considered same larger 28 common pharmaceuticals, by using more robust ab initio methods. While overall trends new data corroborate many results et al., refined view nature present scoring function based on molecular moment strength electric field above arene.