Energy landscapes of conformationally constrained peptides

摘要

Confonnation constraints are known to affect the flexibility and bioactivity of peptides. In this study we analyzed the effect of confonnation constraints on the topography of the energy landscapes of three analogous hexapeptides. The three analogs vary in the degree of constraint imposed on their confonnational motion: linear alanine hexapeptide with neutral tenninals (Ala6), linear alanine hexapeptide with charged terminals (chrg-Ala6), and cyclic alanine hexapeptide (cyc-Ala6). It was found that significantly different energy landscapes characterize each of the three peptides, leading to different folding behaviors. Since all three analogs would be encoded by the same gene, these results suggest that nongenomic post-translational modifications may play an important role in detennining the properties of proteins as well as of their folding pathways. In addition, the present study indicates that the complexity of those energy landscapes that are dominated by funnel topography can be captured by one or two reaction coordinates, such as confonnational siffiilarity to the native state. However, for more complex landscapes characterized by multiple basins such a description is insufficient. This study also shows that similar views of the landscape topography were obtained by principal component analysis (based only on local minima) and by topological mapping analysis (based on minima and barrier infonnation). Both methods were able to resolve the complex landscape topographies for all three peptides.