Cation-Pi interactions as short range molecular staples
This is a more technical post, but may be of interest to those working in biophysics
I have a preconceived notion of the relative strengths of non-bonded inter-atomic interactions. In my mind, electrostatics trumps all - an idea (as far as I can tell, anyway) shared by many. Charge-charge interactions are long range and strong. They drive the formation of well defined interactions in folded proteins through salt bridges and in disordered proteins via more nebulous electrostatically driven conformational preference. Cation-pi interactions, on the other hand - I had thought - were shorter range geometrically constrained interactions of intermediate strength which can be important but ultimately are orders of magnitude weaker than electrostatic interactions.
As it turns out, not so!
In this  recent paper, Kim et al. demonstrate that two like-charged polymers (poly-cations) can undergo phase separation through complex coacervation, where the driving force for this phase separation is many cation-pi interactions. In other words, multivalent cation-pi interactions are strong enough to overcome the electrostatic repulsion of these two liked-charged polymers. From an enthalpy-entropy standpoint this has a whole bunch of really interesting implications that I won't go into, but the take away is that cation-pi interactions are actually pretty strong!
From an evolutionary perspective this actually makes sense - the polymers in question are mimics of proteins secreted by sessile sea creatures (e.g. muscles, scallops etc.) and are basically a super-strong adhesive glue that helps attach the creature's shell to rocks in the ocean. Clearly this natural glue has to be water-proof (given sea creatures live in the sea), but must also be able to withstand wild fluctuations in environment (tides mean that these shells are in both dry and wet environments) as well as be resistant to the ocean's high salinity. Electrostatics are always going to be sensitive to the impact of salt, and while cation-pi interactions are too, the results from this paper would suggest they're far less sensitive than a more conventional electrostatic interaction would be.
While further work remains to be done, there's lots of evidence that aromatic residues play a critical roll in driving liquid-liquid phase separation of disordered proteins through cation-pi interactions. Clearly this has implications for physics-based modeling (notably for fixed charged models which will often underestimate this interaction strength) as well as a more general theoretical description of the driving forces for phase separation.
We featured this paper in the March issue of the IDP State Letter, a monthly newsletter I help set up about a year ago. Organized through the Biophysical Society's IDP subgroup, the IDP State Letter highlights interesting research in the field of Intrinsically Disordered Proteins. If this sounds like something you'd be interested in, please think about signing up!
 Complexation and coacervation of like-charged polyelectrolytes inspired by mussels
Kim S, Huang J, Lee Y, Dutta S, Yoo HY, Jung YM, Jho Y, Zeng H, Hwang DS
Proc. Natl. Acad. Sci. U. S. A. 113, E847–53 (2016).