Non-native interactions underpin the reverse hydrophobic effect. Representative unfolded conformations (right) based on PDB structures (left) were simulated using a coarse-grained continuum chain model that allows sequence-dependent non-native hydrophobic interactions . (a) An unfolded conformation (right) of a double mutant of the Fyn SH3 domain (PDB 1shf) containing a non-native contact between positions 40 and 53 as implicated by DMC . (b-d) Residue positions in red are known experimentally to contribute to the reverse hydrophobic effect [6,8,9]. Those in black or blue are their most likely unfolded-state non-native interacting partners in our simulations. (b) The H1P variant of bacterial immunity protein Im9 (PDB 1imq) , non-native contact Ile17-Val37. (c) Chemotactic protein CheY (PDB 3chy) , Phe14-Met85. (d) λ Cro repressor (PDB 5cro), which unfolds from a dimer to two monomer chains , Tyr26-Leu42 and Tyr26-Tyr51. Question marks in (b-d) emphasize that the predicted non-native interactions are yet to be tested by experiment.
Chan and Zhang Journal of Biology 2009 8:27 doi:10.1186/jbiol126