Conspectus The image is not the thing. Just as a pipe rendered in an oil painting cannot be smoked, quantum mechanical coupling pathways rendered on LCDs do not convey electrons. The aim of this Account is to examine some of our recent discoveries regarding biological electron transfer (ET) and transport mechanisms that emerge when one moves beyond treacherous static views to dynamical frameworks. Studies over the last two decades introduced both atomistic detail and macromolecule dynamics to the description of biological ET. The first model to move beyond the structureless square-barrier tunneling description is the Pathway model, which predicts how protein secondary motifs and folding-induced through-bond and through-space tunneling gaps influence kinetics. Explicit electronic structure theory is applied routinely now to elucidate ET mechanisms, to capture pathway interferences, and to treat redox cofactor electronic structure effects. Importantly, structural sampling of proteins provides an understanding of how dynamics may change the mechanisms of biological ET, as ET rates are exponentially sensitive to structure. Does protein motion average out tunneling pathways? Do conformational fluctuations gate biological ET? Are transient multistate resonances produced by energy gap fluctuations? These questions are becoming accessible as the static view of biological ET recedes and dynamical viewpoints take center stage. This Account introduces ET reactions at the core of bioenergetics, summarizes our team’s progress toward arriving at an atomistic-level description, examines how thermal fluctuations influence ET, presents metrics that characterize dynamical effects on ET, and discusses applications in very long (micrometer scale) bacterial nanowires. The persistence of structural effects on the ET rates in the face of thermal fluctuations is considered. Finally, the flickering resonance (FR) view of charge transfer is presented to examine how fluctuations control low-b Studies over the last two decades introduced both atomistic detail and macromolecule dynamics to the description of biological ET. The first model to move beyond the structureless square-barrier tunneling description is the Pathway model, which predicts how protein secondary motifs and folding-induced through-bond and through-space tunneling gaps influence kinetics. Explicit electronic structure theory is applied routinely now to elucidate ET mechanisms, to capture pathway interferences, and to treat redox cofactor electronic structure effects. Importantly, structural sampling of proteins provides an understanding of how dynamics may change the mechanisms of biological ET, as ET 51 − 54 Quantum chemistry is now used widely to explore even more refined questions about tunneling mediation, 31 , 32 , 43 as tunneling pathways appear in bundles or tubes in proteins and the multitude of paths interfere with one another. Indeed, theoretical analysis and extensive experimental data support the view that secondary structure and atomic details of pathway structure set the average β value for tunneling decay in proteins, producing structure-specific rates as discussed next. A crucial and nuanced question is, under what circumstances do tunneling pathways limit ET rates in proteins? That is, does thermal motion erase pathway structure effects? Apparently heme protein folding tends to insulate the axial heme pathways from the protein surface. This causes anomalously slow ET rates (for their distance) in specific ruthenated myoglobin, cytochrome c , and cytochrome b 562 derivatives. 26 , 31 The other 85% of the derivatives have rates that can be predicted from knowledge of their bridging secondary structure, without zooming in to examine pathway structure at full atomistic resolution. Of course, comparisons among proteins with different cofactors require detailed quantum chemical analysis since the coupling pre-exponential factors are different for flavins, blue coppers, hemes, FeS clusters, redox active tryptophan residues, etc. 2.4. Water Pathways in ET and PCET Tunneling can certainly be mediated by water at protein–protein interfaces and in clefts. 56 Our studies of self-exchange ET indicate that thin water layers at protein–protein interfaces can establish multiple constructively interfering pathways that enhance ET. For azurin dimers, the interplay of water-mediated pathways was interpreted in terms of electrostatically driven structuring of those pathways. 37 Indeed, rates accelerated by such effects could be larger than predicted by tunneling estimates based on frozen water models. 22 Recent studies also point to a possible role for structured water in PCET. Pathway structures fluctuate, although pathway-coupling effects discussed above are often analyzed in fixed protein geometries. Consider a protein ET system with structure that partially unfolds and refolds on the time scale of ET (see Figure 1 ). In this case, one expects the mean-squared coupling to represent the average tunneling characteristics of the medium and the pathway effects to be ensemble averaged. Do protein fluctuations wash out all sequence and folding effects on ET couplings; does a protein’s time-averaged structure control its ET coupling? We have addressed these questions by performing D–A coupling analysis on protein geometries sampled along classical MD trajectories. Static reduced dimensional views, like Magritte’s rendering in the Conspectus, have tremendous value but do not convey the richness of the three-dimensional, dynamical, functional object. Experimental studies increasingly indicate the importance of fine quantum effects in biological systems, associated with coherences on the nanometer length scale. Elucidating the physics and biochemistry of these subtle effects requires theoretical frameworks to describe the quantum dynamics with as few ad hoc mechanistic assumptions as possible, while taking the nature of the fluctuations into account.