van der Waals Forces in Biomolecular Systems: from Solvation to Long-range Interaction Mechanisms

One decisive characteristic of the biomolecular machinery is the access to a rich set of coordinated processes within a small energy window. Most of these processes involve collective conformational changes and occur in an aqueous environment. Conformational changes of (bio)molecules as well as their interaction with water are thereby largely governed by non-covalent van der Waals (vdW) dispersion interactions. By virtue of their intrinsically collective nature, vdW forces also represent a key influence on collective nuclear behavior. Our understanding of vdW interactions in large-scale (bio)molecular systems, however, is still rather limited [Chem. Soc. Rev. 2019, 48, 4118]. Here, we employ the Many-Body Dispersion framework to investigate the vdW interaction in biomolecular systems and its spatial and spectral aspects. In particular, we show the role of beyond-pairwise vdW forces for protein stability and highlight the delocalized character of the protein-water vdW interaction. We further examine intermolecular electronic behaviors and reveal a coexistence of strong delocalization with spatially-separated yet correlated, local domains. This, ultimately, forms the basis for a potential, efficient long-range interaction mechanism for coordinated processes in biomolecular systems.