Unfolded state of peptides.

Publisher Summary This chapter illustrates the current knowledge on the unfolded state of peptides. Currently, the characterization of the populated microscopic states of a peptide is possible only by simulation methods. The focus is on molecular dynamics simulations of spontaneous (i.e., lacking biasing potentials or directed-sampling algorithms) and reversible folding of peptides in solution (i.e., with explicit solvent molecules), since the results from this type of studies are the least dependent on the methodology. A full characterization of the unfolded state becomes as essential as the determination of the folded conformation in two scenarios. The first is in the study of the physical, chemical, and biological properties of peptides. The folded conformation of a peptide is, in general, only marginally more stable than the lowest-free-energy unfolded conformation. As a result, any macroscopic observable of a peptide is weighted with both the folded and the unfolded states. Interpreting such observables in terms of the folded conformation only is therefore not correct. The second scenario is related to the study of peptide and protein folding. The description of equilibrium requires knowledge about each of the states involved. Therefore, it is fundamental to describe not only the folded state but also the unfolded state accurately in order to draw conclusions on the nature and mechanisms of peptide and protein folding.