Peptides are essential to life, playing important roles in many biological processes. Understanding the conformational changes peptides go through is crucial for understanding their function and as models for the folding of protein processes. The conformational space of a peptide is influenced by many factors, including amino acid sequence, solvent environment, and temperature. This work examines the effects of peptide sequence and temperature on the conformational space of short, five- and six-amino acid long peptides. The first peptide sequences chosen were selected from peptides synthesized in the Advanced Organic Chemistry laboratory at Northern Arizona University and found to have multiple conformational states through NMR analysis. These states are stabilized by interactions between side chains of the amino acids, including hydrogen bonding, aromatic interactions, and van der Waals interactions. The amino acid proline is particularly important for observing multiple conformational states and even isomerization of the backbone. In the vicinity of proline, there is usually a lower activation energy to transition to a cis state and therefore the backbone is more likely than other amino acids to isomerize. Once sequences were chosen based off of these interactions, the structure of these peptides were analyzed using molecular dynamics (MD) simulations by examining radius of gyration and omega angles of the peptide backbone. From the sequences that demonstrated two conformations, a genetic algorithm was used to generate new sequences that result in multiple conformations. These peptides were then synthesized in the lab using solid-phase peptide synthesis. They were analyzed using 1H and 13C NMR spectroscopy to verify sequence and the number of conformational states. The interactions of side chains have demonstrated a large impact on conformational changes, particularly hydrogen bonding and aromatic interactions. This work reveals the sequence patterns prone to multiple confirmations and identifies specific molecular mechanisms that stabilize these structures.

Searching for peptides that fold into interesting conformations: Combined experimental and computational study

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.