Energetic networks of lone pair–π interactions in phycobiliprotein interfaces: Structural organization, geometry and cooperative stabilization Scientific paper

Abstract

Lone pair–π interactions represent an underexplored class of noncov­alent forces in protein architecture, despite their fundamental electronic signific­ance. Here, we present a comprehensive computational and bioinformatics ana­lysis of lone pair–π interactions at phycobiliprotein interfaces based on 20 high-resolution X-ray crystal structures. Using defined geometric criteria and ab ini­tio quantum-chemical calculations at the LMP2/cc-pVTZ++ level on reduced molecular models, we systematically characterized their distribution, geometry, topology and energetic contributions. We identified 2,245 lone pair–π interactions, revealing a highly non-random and chemically selective interaction landscape dominated by oxygen-based lone pair donors and aromatic π acceptors, particularly Tyr and Phe. Geometric analysis showed strong distance and angular preferen­ces, consistent with directional donor–acceptor orbital interactions rather than nonspecific packing effects. Energy calculations revealed a structured interac­t­ion potential surface, with stabilizing energies clustering in the −0.1 to −5.0 kJ mol^-1 range within defined geometric domains. Network analysis further demon­strated that more than half of the interactions participate in cooperative, furcated lone pair–π motifs, generating interfacial stabilization through multivalent inter­action networks. Collectively, these results establish lone pair–π interactions as geometry-encoded, energetically selective and cooperatively organized stabil­izing elements that contribute to interfacial specificity, structural precision and quaternary structure stability in phycobiliprotein assemblies.