Determining the principal energy-transfer pathways responsible for allosteric communication in biomolecules remains challenging, partially due to the intrinsic complexity of the systems and the lack of effective characterization methods. In this work, we introduce the eigenvector centrality metric based on mutual information to elucidate allosteric mechanisms that regulate enzymatic activity. Moreover, we propose a strategy to characterize the range of correlations that underlie the allosteric processes. We use the V-type allosteric enzyme imidazole glycerol phosphate synthase (IGPS) to test the proposed methodology. The eigenvector centrality method identifies key amino acid residues of IGPS with high susceptibility to effector binding. The findings are validated by solution NMR measurements yielding important biological insights, including direct experimental evidence for interdomain motion, the central role played by helix h$\alpha 1$, and the short-range nature of correlations responsible for the allosteric mechanism. Beyond insights on IGPS allosteric pathways and the nature of residues that could be targeted by therapeutic drugs or site-directed mutagenesis, the reported findings demonstrate the eigenvector centrality analysis as a general cost-effective methodology to gain fundamental understanding of allosteric mechanisms at the molecular level. Significance Allosteric processes are ubiquitous in macromolecules and regulate biochemical information transfer between spatially distant sites. Despite decades of study, allosteric processes remain generally poorly understood at the molecular level. Here, we introduce the eigenvector centrality measure of mutual information to disentangle the complex interplay of amino acid interactions giving rise to allosteric signaling. The analysis of eigenvector centrality is tested in imidazole glycerol phosphate synthase (IGPS), a prototypical V-type allosteric enzyme. The resulting insights allow us to pinpoint key amino acids in terms of their relevance in the allosteric process, suggesting protein-engineering strategies for control of enzymatic activity.

Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with a data-driven approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. While we cannot rule out the existence of alternative non-aromatic fluorescence mechanisms in other systems, we demonstrate that this carbonyl-lock mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and set the stage for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics.

The influence of the environment on the functionality of the oxygen-evolving complex (OEC) of photosystem II has long been a subject of great interest. In particular, various water channels, which could serve as pathways for substrate water diffusion, or proton translocation, are thought to be critical to catalytic performance of the OEC. Here, we address the dynamical nature of hydrogen bonding along the water channels by performing molecular dynamics (MD) simulations of the OEC and its surrounding protein environment in the S₁ and S₂ states. Through the eigenvector centrality (EC) analysis, we are able to determine the characteristics of the water network and assign potential functions to the major channels, namely that the narrow and broad channels are likely candidates for proton/water transport, while the large channel may serve as a path for larger ions such as chloride and manganese thought to be essential during PSII assembly.