Molecular Dynamics Simulations

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 notably 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 prior to computational studies.

Yaku’amide presents itself as a prototypical example of such cases because 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 simulations are advantageous when modeling peptides containing exotic amino acids, such as dehydroamino acids, because they achieve an ideal balance between resource allocation and computational accuracy.

Related Publications:
Ashraf, N. M., Krishnagopal, A., Hussain, A., Kastner, D. W., Mahmoud, A., Sayed, M., Mok, Y., Swaminathan, K., Zeeshan, N. “Engineering of serine protease for improved thermostability and catalytic activity using rational design” Int. J. Biol. Macromol. 126(229-237), (2019).