I finished the review of "Biological Physics" today, which included the sections on bioenergetics, forces, and single-molecule experiments. I skipped the section on reaction theory because I am not familiar with the topic and it didn't interest me as much as the others.
There are two primary topics in bioenergetics at the biomolecular level: charge transport and light transduction. Charge transport refers to the process by which isolated charges travel amongst different sites in a complex molecule. This process is inherently quantum mechanical, since electrons and holes may actually tunnel into different sites in the molecule, depending on the molecule's conformation.
Light transduction refers to the conversion of energy in a photon to chemical or electronic energy. A paragraph is dedicated to human vision and the photo-induced isomerization that is central to its operation, but the rest of this sub-section is devoted to photosynthesis.
During photosynthesis, "antenna systems" in the chlorophyll molecules capture light energy, which is transferred to other parts of the plant cell along excited molecular states, much like in Foerster resonance energy transfer. The transfer is so fast that the quantum mechanical coherence of the excited states likely plays a role. It seems that most of the work done up to the point in time when the article was written has been performed by theorists.
The various forces in the cell are typically "effective" forces models typically neglect the fundamental electromagnetic nature of the primary forces in the cell. At the protein level, enzymes may actually pull apart the covalent bonds in "violent" events. It's also been hypothesized that mechanical vibrations in the form of solitons can propagate along the covalently-bonded protein backbone, but this is strongly debated.
The transmission of forces through a heterogeneous medium, like the cell membrane is also a topic of study.
Finally, single-molecule studies are gaining prominence as experimental techniques become more refined, but "the challenge of studying individual protein molecules is still very much in its infancy... The key is to use extreme dilution so that only a single biomolecule is in the reaction volume."
Much single-molecule work has been done on DNA because it is simple and readily obtained. Spring-like forces in DNA are both enthalpic, which means they depend on the energy change due to deformation of electronic orbitals, and entropic, which means the DNA resists changing its shape due to interaction with its thermal environment.
In the conclusion, the authors anticipate that problems relating to the brain lie ahead as major areas of work in biological physics.
It would seem that the experimental study of proteins remains a major challenge to biological physics, but also is perhaps the most worthwhile to pursue. Photosynthesis, the effects of a protein's environment on its folding and charge transport, disordered protein behavior, and the forces between parts of proteins are not very well-understood. If there are new discoveries to be made, then I think they lie in protein dynamics.