Quantum Mechanics of Proteins in Explicit Water: The Role of Plasmon-Like Solute-Solvent Interactions

Abstract

Quantum-mechanical van der Waals dispersion interactions play an essential role for both intra-protein and protein-water interactions -- the two main driving forces for the structure and dynamics of proteins in aqueous solution. Typically, these interactions are only treated phenomenologically via pairwise potential terms in classical force fields. Here, we use an explicit quantum-mechanical approach based on density-functional tight-binding with the many-body dispersion formalism, which allows us to demonstrate the unexpected relevance of the many-body character of dispersion interactions for protein energetics and the protein-water interaction. In contrast to commonly employed pairwise approaches, many-body effects significantly decrease the relative stability of the native state in the absence of water. In an aqueous environment, the collective character of the protein-water van der Waals interaction counteracts this effect and stabilizes native conformations and transition states. This stabilization arises due to a high degree of delocalization and collectivity of protein-water dispersion interactions, suggesting a remarkable persistence of long-range electron correlation through aqueous environments. Our findings are exemplified on prototypical showcases of proteins forming $\beta$-sheets, hairpins, and helices, emphasizing the crucial role of plasmon-like solute-solvent interactions in biomolecular systems.