Dissecting Entropic Coiling and Poor Solvent Effects in Protein Collapse

Abstract

The early events in protein collapse and folding are guided by the protein's elasticity. The contributions of entropic coiling and poor solvent effects like hydrophobic forces to the elastic response of proteins are currently unknown. Using molecular simulations of stretched ubiquitin in comparison with models of proteins as entropic chains, we find a surprisingly high stiffness of the protein backbone, reflected by a persistence length of 1.2 nm, which is significantly reduced by hydrophobic forces acting between protein side chains to an apparent persistence length of 0.3-0.6 nm frequently observed in single-molecule stretching experiments. Thus, the poor solvent conditions of a protein in water lead to a protein compaction much beyond the coiling of an entropic chain and thereby allow a protein to appear softer than when using good solvents.

Dynamic Modulation of Fimbrial Extension and FimH-Mannose Binding Force on Live Bacteria Under pH Changes: A Molecular Atomic Force Microscopy Analysis

“…The lowest l p value further matches the typical pitch distance for a -helix while the second value adequately compares to the typical pitch distance for an -helix 36, 37 or -13 helix rise per amino acids. [38][39][40] This result is in good agreement with conformation of the fimbrial subunits that are characterized by -sheet for FimH (Ig-like domains) whereas the stacking of FimA leads to formation of -helix structure. Altogether, the above results indicate that the obtained persistence length that reflects the very flexibility of the FimH adhesin, is not affected with increasing pulling rates at fixed solution pH.…”

How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory

“…Investigations by several theoretical groups (40)(41)(42)(43) have suggested that a hydrophobic polymer in solution will collapse into a surface area-minimized globule (such as those seen by AFM scans; see Fig. 1A) and that forcing a part of the polymer into solution causes the polymer to assemble into coexisting chain and globule regions (Fig.…”

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

“…This roughly corresponds to the length of a single amino acid. However, in more recent studies it has been suggested that this measured value of p accounts for both entropic and attractive interactions due to hydrophobic contacts within a protein [100].…”