Peptides unfolded states

In the native protein these less stable ds-proline peptides are stabilized by the tertiary structure but in the unfolded state these constraints are relaxed and there is an equilibrium between ds- and trans-isomers at each peptide bond. When the protein is refolded a substantial fraction of the molecules have one or more proline-peptide bonds in the incorrect form and the greater the number of proline residues the greater the fraction of such molecules. Cis-trans isomerization of proline peptides is intrinsically a slow process and in vitro it is frequently the rate-limiting step in folding for those molecules that have been trapped in a folding intermediate with the wrong isomer. 

In the unfolded state, the peptide chain and its R groups interact with solvent water, and any measurement of the free energy change upon folding must consider contributions to the enthalpy change (AH) and the entropy change (A.S) both for the polypeptide chain and for the solvent ... 

Turning now to the chapters in this volume, a variety of complementary techniques and approaches have been used to characterize peptide and protein unfolding induced by temperature, pressure, and solvent. Our goal has been to assemble these complementary views within a single volume in order to develop a more complete picture of denatured peptides and proteins. The unifying observation in common to all chapters is the detection of preferred backbone conformations in experimentally accessible unfolded states. 

Three theory papers are also included. Determinants of the Polyproline II Helix from Modeling Studies by Creamer and Campbell reexamines and extends an earlier hypothesis about Pn and its determinants. Hydration Theory for Molecular Biophysics by Paulaitis and Pratt discusses the crucial role of water in both folded and unfolded proteins. Unfolded State of Peptides by Daura et al. focuses on the unfolded state of peptides studied primarily by molecular dynamics. 

In Section III, a distinction is made between experimental conformation and folded conformation. Thus, the most populated conformation of a peptide is identified as the folded conformation, irrespective of experimental or secondary-structure considerations. The folded state is then associated to the folded or most populated conformation, while the unfolded state embodies all other conformations and includes any other substates. 

The unfolded states of eight different peptides, sampled in a corresponding number of molecular dynamics simulations of reversible peptide folding in solution under equilibrium conditions, are analyzed in this section (see Table I). 

In native collagen, all Gly-Pro and Xaa-Hyp peptide bonds are in the trans conformation, whereas in the unfolded state, a significant fraction of cis isomers populates at each Gly-Pro and Xaa-Hyp peptide bond, cis-to-trans isomerization reactions at prolyl peptide bonds are the origin for the observed slow kinetics of triple helix formation" as shown by their high activation energy ( 72 kj moG )" and their acceleration by prolyl... 

Most proteins fold spontaneously into their native conformation, even in the test tube. In the cell, where there are very high concentrations of proteins (around 350 g L ), this is more dif cult. In the unfolded state, the apolar regions of the peptide chain (yellow) tend to aggregate—due to the hydrophobic effect (see p. 28)—with other proteins or with each other to form insoluble products (2). In addition, unfolded proteins are suscep-... 

---