(426a) Computational Investigation of the Effect of Backbone Chiral Inversions on Protein Folding
- Conference: AIChE Annual Meeting
- Year: 2018
- Proceeding: 2018 AIChE Annual Meeting
- Group: Engineering Sciences and Fundamentals
- Time: Tuesday, October 30, 2018 - 3:30pm-3:45pm
In addition to helical polyalanine peptides, we also study the hairpin peptide, GB1 hairpin, with systematic chiral inversions in explicit water. In contrast to the helical peptide, we do not find a monotonic change in the structure content, i.e. Î²-sheet content, along the perturbation coordinate, given by the number of L- to D-inversions. The effects of L- to D-inversions are rather position-specific for this hairpin peptide. Some inversions yield a similar or higher secondary structure content compared to the homochiral hairpin, in contrast to the helical peptide. However, similarity in secondary structure content does not imply fold similarity: we have in fact observed cases in which the peptide with inversions folds into clearly different hairpin structures with respect to the non-chirally-perturbed (native) peptide, while sharing similar secondary structure content. In other words, the chirally perturbed hairpin peptides fold into different unique structures when they are still able to fold. Therefore, our main conclusion applies to both of the structurally distinct proteins we examined, namely, that arbitrary heterochirality conspires against proper folding.