Stabilization of the Protein Structure by the Many-Body Cooperative Effect in the NH/π Hydrogen-bonding Tryptophan...

The indole ring of tryptophan can form NH/π hydrogen bonds, acting both as a hydrogen donor at the NH group in the pyrrole subring and as a hydrogen acceptor at the benzene subring. In the structural core of the trimeric stable protein Pholiota squarrosa lectin (PhoSL), three indoles are symmetrically arranged and form NH/π hydrogen bonds among each other. Here, we conducted quantum chemical calculations on this indole triad by using various methods and basis sets. The analyses revealed cooperativity in triad formation, with the many-body effect contributing approximately -2 kcal mol^-1, which significantly stabilizes this protein. Symmetry-adapted perturbation theory ascribed this effect to the induced polarization. The electrostatic potential and atomic charges indeed revealed a charge redistribution through the NH/π hydrogen bond, which was favorable for triad formation.