Dissecting Entropic Coiling and Poor Solvent Effects in Protein Collapse

Protein folding to specific functional structures is preceded by a largely unspecific protein collapse into a molten globule state which reflects protein elasticity. Contributions to protein elasticity, however, are not yet well understood. Experimental measurements on single protein chains using force spectroscopy reveal a force-extension behavior in reasonable agreement with polymer random coil models such as the worm-like chain model (WLC).1 WLC fits to such data yield an effective persistence length in the range peff) 0.3-0.6 nm (Figure 1a)2,3 as a measure of protein elasticity, in agreement with end-to-end distances of loops in protein structures.4 Surprisingly, recent measurements at low force again do not reveal any departure from purely entropic chain behavior.5 Consequently, a major effort has been focused on the development of theories for protein elasticity solely based on chain entropy,6,7 with departures from entropic coiling behavior only considered a