Investigating van der Waals Collective Behavior in Proteins via Interaction with Polarizable Ligands

The assembly of complex macromolecular biological systems is often driven by weak non-covalent vdW dispersion interactions arising from electrodynamic correlations between instantaneous charge fluctuations in matter. Variations in these power laws can have a profound impact on observed properties. Here, we computationally investigate the effect of chemically unreactive ligands that act on proteins mainly via vdW dispersion forces. Specifically, we use inhalational anesthetics. While the exact mechanisms of anesthetic action are unknown, there is a known link between anesthetic potency and solubility in a non-polar medium. Anesthetic action is also related to an anesthetic’s hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in non-polar regions within brain proteins. We use quantum chemistry calculations, and theoretical modeling of collective dipole interactions in proteins to investigate the effect of anesthetic gases on protein dynamics. In general these gases alter collective terahertz dipole oscillations. Our results emphasize the importance of collective electronic vibrational motions in proteins, how such motions contribute to overall protein interaction, and how interaction with polarizable ligands may alter such motions and interactions.