Notes on "Biological Physics," Part I

There is an article from 1999 in Reviews of Modern Physics entitled "Biological Physics." This review summarizes research during the twentieth century where "physics has influenced biology and where investigations on biological systems have led to new physical insights." The exchange of ideas between the two fields has not been of equal magnitude, the authors note. Many tools from physics have found their way into the biological sciences, though some biological systems have led to new physics, usually in the form of providing experimental testbeds for new physical theories. The article is primarily concerned with molecular biological physics.

The seven primary sections of the review are

1. The structures of biological systems
2. Complexity in biology
3. Dynamics, mostly within proteins
4. Reaction theory, where biology has provided testbeds for new physical theories
5. Bioenergetics
6. Forces
7. Single-molecule experiments.

Most of the interesting ideas I've found so far in the article are associated with the complexity and dynamics of biomolecules. Particularly, there is an idea known as the principle of minimal frustration. From the Wikipedia article,

"This principle says that nature has chosen amino acid sequences so that the folded state of the protein is very stable. In addition, the undesired interactions between amino acids along the folding pathway are reduced making the acquisition of the folded state a very fast process. Even though nature has reduced the level of frustration in proteins, some degree of it remains up to now as can be observed in the presence of local minima in the energy landscape of proteins."

This idea came from a theory of energy landscapes for proteins that was developed by Bryngelson and Wolynes. In language that I'm more familiar with, the potential energy of the molecules has some fractal-like structure, because from Section III in the article the authors state that

"The kinetic observations suggest that the energy landscape might have a hierarchical structure, arranged in a number of tiers, with different tiers having widely separated average barrier heights."

It seems like structural determination of proteins and other biomolecules has become something akin to bookkeeping. The tools exist and are refined to find static structures, like neutron scattering and NMR. Additionally, the energy landscape theory for protein folding seems to be mature at this point as well. So what open-ended questions still exist in biological physics? After reading up to section V, I've compiled the following grand problems in biological physics as I've interpreted them from this paper only:

1. "A synthesis that connects structure, energy landscape, dynamics, and function has not yet been achieved." This seems to suggest that there is some degree of incoherence between these individual fields of study, so ideas that link them together are required.
2. Biochemists can now synthesize their own proteins, but can they do this in a useful manner, for, say, molecular and microscopic engineering purposes?
3. Sensing and characterizing phase transitions, especially in glassy systems, could lead to better experimental investigations into protein folding.
4. "Understanding protein folding can improve the capability of predicting protein structure from sequence." Apparently there's a lot of DNA sequence information, but predicting what proteins come from it is nontrivial.