  The solvent quality determines the collapsed or the expanded state of a
polymer. For example, a polymer dissolved in a poor solvent collapses, whereas
in a good solvent it opens up. While this standard understanding is generally
valid, there are examples when a polymer collapses even in a mixture of two
good solvents. This phenomenon, commonly known as co-non-solvency, is usually
associated with smart polymers. Moreover, recent experiments have shown that
the elastin-like polypeptides (ELPs) show co-non-solvency behavior in
aqueous-ethanol mixtures. In this study, we investigate the phase behavior of
ELPs in aqueous binary mixtures using molecular dynamics simulations of
all-atom and complementary explicit solvent generic models. The model is
parameterized by mapping the solvation free energy obtained from the all-atom
simulations onto the generic interaction parameters. For this purpose, we
derive segment based generic parameters for four different peptides, namely
proline (P), valine (V), glycine (G) and alanine (A). Here we compare the
conformational behavior of two ELP sequences, namely VPGGG and VPGVG, in
aqueous-ethanol and -urea mixtures. Consistent with recent experiments, we find
that ELPs show co-non-solvency in aqueous-ethanol mixtures. Ethanol molecules
have preferential binding with all ELP residues and thus driving the
coil-to-globule transition. On the contrary, ELP conformations show weak
variation in aqueous-urea mixtures. Our simulations suggest that the glycine
residues dictate the overall behavior of ELPs in aqueous-urea, where urea
molecules have a rather weak preferential binding with glycine, i.e., less than
kT. While the validation of the latter findings will require more detailed
experimental investigation, the results presented here may provide a new twist
to the present understanding of cosolvent interactions with peptides and
proteins.
