Burial of Hydrocarbon Causes Cooperative Enhancement of Electrostatic Binding

The introduction of alanine methyl groups in adjacent positions on a peptide ligand results in a cooperative enhancement of electrostatic binding from the burial of hydrocarbon. This observation may explain why larger changes in free energy occur when hydrocarbon substituents are buried in a molecular recognition site than can be accounted for by the solvent transfer model (classical hydrophobic effect).