Helix Formation by Alanine-Based Peptides in Pure Water and Electrolyte Solutions: Insights from Molecular Dynamics Simulations

Specific ion effects on oligopeptide conformations in solution are attracting strong research attention, because of their impact on the protein-folding problem and on several important biological–biotechnological applications. In this work, we have addressed specific effects of electrolytes on the tendency of oligopeptides toward formation and propagation of helical segments. We have used replica-exchange molecular dynamics (REMD) simulations to study the conformations of two short hydrophobic peptides [Ace-(AAQAA)₃-Nme (AQ), and Ace-A₈-Nme (A8)] in pure water and in aqueous solutions of sodium chloride (NaCl) and sodium iodide (NaI) with concentrations of 1 and 3 M. The average helicities of the AQ peptide have been analyzed to yield Lifson–Roig (LR) parameters for helix nucleation and helix propagation. The salt dependence of these parameters suggests that electrolytes tend to stabilize the helical conformations of short peptides by enhancing the <i>helix nucleation</i> parameter. The helical conformations of longer oligopeptides are destabilized in the presence of salts, however, because the <i>helix propagation</i> parameters are reduced by electrolytes. On top of this general trend, we observe a significant specific salt effect in these simulations. The hydrophobic iodide ion in NaI solutions has a high affinity for the peptide backbone, which reflects itself in an enhanced helix nucleation and a reduced helix propagation parameter with respect to pure water or NaCl solutions. The present work thus explains the computational evidence that electrolytes tend to stabilize the compact conformations of short peptides and destabilize them for longer peptides, and it also sheds additional light on the specific salt effects on compact peptide conformations

Self-Assembly of an Aspartate-Rich Sequence from the Adenovirus Fiber Shaft: Insights from Molecular Dynamics Simulations and Experiments

The self-assembly of short peptides into fibrous nanostructures (such as fibrils and tubes) has recently become the subject of intense theoretical and experimental scrutiny, as such assemblies are promising candidates for nanobiotechnological applications. The sequences of natural fibrous proteins may provide a rich source of inspiration for the design of such short self-assembling peptides. We describe the self-assembly of the aspartate-rich undecapeptide (NH₃⁺-LSG­SDS­DTL­TV-NH₂), a sequence derived from the shaft of the adenovirus fiber. We demonstrate that the peptide assembles experimentally into amyloid-type fibrils according to widely accepted diagnostic criteria. In addition, we investigate an aqueous solution of undecapeptides by molecular dynamics simulations with an implicit (GB) solvent model. The peptides are frequently arranged in intermolecular β-sheets, in line with their amyloidogenic propensity. On the basis of both experimental and theoretical insights, we suggest possible structural models of the fibrils and their potential use as scaffolds for templating of inorganic materials