Implications of Tight Packing

Cell proteins are incredibly tightly packed in vivo. According to a paper due to be published in PNAS later this month, the estimated spatial density is around 43%. I can't help noting that this is not far from Kepler's ball-packing optimum of 74%, which (if my math is correct) ultimately means that proteins are separated by well under one protein-radius; viz., the average inter-protein distance is probably a few van der Waals radii; enough for a solvation shell and not much more. (Note to self: If proteins are packed shoulder-to-shoulder, what are the implications for nearest-neighbor hydrophobic interactions? Can neighbor proteins interfere with "hydrophobic collapse" of a protein that's in the process of folding?)

The authors of the PNAS paper, who used apoflavodoxin in their study, note that crowding (as simulated in silico, as well as in vitro, in a separate experiment) "made the native state of the protein 20 degrees Celsius more resistant to thermal perturbations."

The authors also found that "The secondary structure of the folded protein increased by as much as 25 percent based on circular dichroism data."

Perhaps at least some MD-simulation studies of protein folding should be repeated with and without crowding?