The article reviews recent developments and applications for predicting the standard reduction potentials of chemical reactions in solution.

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.

Continuum solvent calculations of pK_as and reduction potentials usually entail the use of a thermodynamic cycle to express the reaction free energy in terms of gas phase energies and free energies of solvation.