Origin of the sequence-dependent polyproline II structure in unfolded peptides.
Recent studies have indicated that the unfolded states of polypeptides contain a substantial amount of polyproline type II (P(II)) structure. This energetically and structurally preorganized state may contribute to the reduction of the folding search, as well as to the recognition of intrinsically unstructured proteins and polyproline ligands. Using Monte Carlo simulations of natively unfolded peptides in the presence of explicit aqueous solvation, we observe that residue-specific P(II) conformational propensity is the result of the modulation of polypeptide backbone hydration by a proximal side-chain. Such a mechanism may be unique among those that contribute to the modulation of secondary structures in proteins. The calculated conformational propensities should prove useful for the development of a configurational P(II) scale necessary for the prediction and design of natural-like polypeptides.
Kentsis
Alex
A
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.
Mezei
Mihaly
M
Osman
Roman
R
D007700:Kinetics; D009010:Monte Carlo Method; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D012997:Solvents; D013816:Thermodynamics
D009842:Oligopeptides; D010455:Peptides; D012997:Solvents; C011083:polyproline