The Nature of Tunneling Pathway and Average Packing Density Models for Protein-Mediated Electron Transfer†

The last 30 years have witnessed the development of increasingly successful theoretical approaches to predicting how a protein's chemical composition and three-dimensional structure influence its propensity to mediate electron-transfer reactions. Analysis has progressed from uniform-barrier models that neglect atomic detail, to pathway models that incorporate the specific nature of the bonding and the protein fold, to multipathway models that add coherently the contributions of pathways, to methods that average over accessible geometries. Large-scale electronic structure methods remain of somewhat limited use because:  the demands of geometry sampling and electronic structure calculation are considerable, especially for slower ET events; qualitative new insights arising from the more intensive analysis have been moderate; and structure−function relations become increasingly difficult to derive from more complex models. For these reasons, simple models remain both useful and popular. The simplest structure...