We study the role of sequence and solvation in shaping the temperature-pressure ($T$, $P$) conformational landscape of model heteropolymers with a coarse-grained model. We design foldable primarily hydrophobic sequences with fixed polar content in water at physiological conditions, which demonstrate ($T$, $P$) dependence of conformational stability similar to biological proteins. Inherent helicity emerges as a result of local polar-polar interactions in the sequences that mimic biological $\alpha$ helices. The helical propensity is reduced upon solvation and remains unaltered at cold $T$ and high $P$, which is driven by the $T$-$P$ induced changes of the hydration shell. Consequently, at nonphysiological conditions the weakening of hydrophobic interactions facilitates population of non-native, helical, compact conformations stabilized through direct nonlocal interactions between polar residues.

• Received 12 January 2013

DOI:https://doi.org/10.1103/PhysRevLett.111.058103