Designing a molecular model for the cytochrome f-plastocyanin molecular interface: Cation-π interactions play an important role in the molecular recognition event

摘要

Blue copper protein plastocyanin and heme protein cytochrome f are physiological partners in the photosynthetic electron transfer chain. Recent computational studies have suggested that the complex of these two proteins is stabilized by a series of intermolecular salt bridges and a cation-π interaction between Tyr83 of plastocyanin and Lys65 of cytochrome f. To investigate the specificity of this interaction, model peptides were constructed and their association constants were determined. Molecular dynamics simulations were carried out to determine the number of salt bridges and cation-π interactions in the model complexes. Only with the addition of a corrective potential for the inductive effect of the cation over the π-ring did molecular dynamics simulations reproduce experimental trends. Using the improved potential, a cyclic peptide was de novo designed and synthesized. This new peptide offers the first experimental evidence for cation-π interactions stabilizing intermolecular complexes. These experiments also demonstrate the importance of correct cation-π interaction descriptions in molecular modeling force fields.