QM/MM Calculations

Yaku’amide A (YA) is an extremely rare peptide that was isolated from the deep-sea sponge Ceratopsion sp. Identification and characterization of this peptide unveiled its curious structural profile and its many non-standard amino acids and most noteablly dehydroamino acids. When tested against an array of 39 human cancer cell lines, YA exhibited notable cytotoxicity against P388 murine leukemia cells via a potentially novel mode of action. Many medically relevant peptides, such as Yaku’amide, often contain non-standard amino acids and require de novo parameters proir to computational studies.

Yaku’amide presents itself as a protypical example of such cases becuase its sequence is almost exclusively non-standard and current research surrounding the molecule would benefit from computational structure-function modelling. One approach to handling complex peptides lacking robust parameters is quantum mechanics (QM)/molecular mechanic (MM) hybrid simulations that rely on AMBER forcefield and DFT calculations. QM/MM silmulations are advantageous when modeling peptides containing exotic amino acids, such as dehydroamino acids, becuase they achieve an ideal balance between resource allocation and computational accuracy.

Related Publications:
Kastner, D. W., Castle, S. L. “ONIOM(DFT:MM) Study of Yaku’amide A and Analogues.” Journal of Undergraduate Research, ORCA Grant (2018).

Kastner, D. W., Ankur, J., Castle, S. L. “Progress Toward Synthetically Simplified Natural Anticancer Peptide.” ScholarsArchive, 2572-4479 (2018).