Novel Anticancer Peptide Design; Computational Point of View

9 TH INTERNATIONAL BAU DRUG DESIGN CONGRESS, İstanbul, Türkiye, 29 Kasım - 02 Aralık 2023, ss.127, (Özet Bildiri)

GLOBOCAN has estimated the number of new cancer cases from 2020 to 2040 will be 30.2

million. Although significant improvements in cancer research, treatments like

chemotherapy and radiotherapy are still limited and have considerable side effects. This has

led to exploring new routes for treatment, like anticancer peptides. These 10-60 amino acid

long positively-charged peptides display distinct mechanisms of action in disrupting

negatively-charged cancer cell membranes while not harming the healthy ones. This study

seeks to design novel anticancer peptides using the unique family of Temporins as templates

[Temporin-1RNa and Temporin-1RNb] and investigate their properties through

computational methods. The AntiCP-2.0 web server was used to generate peptides with

altered amino acids. Novel peptides were evaluated for net charge, anticancer activity, cell -

penetrating activity, hemolytic activity, and hydrophobicity. The best ten novel peptides

were selected for further research. For 2D structure prediction, the PEP2D server and for

3D structure prediction the PEP-FOLD3.5 server was used, and all were predicted as helix.

To glimpse how the peptides respond in water and in a hydrophobic solvent environment,

250 ns molecular dynamics simulations were conducted. RMSD analyses were carried out

after the simulations. In conclusion, while peptides are predominantly in the random form

when water is used as the solvent in the simulations, they acquire a 3D helix form when in

hydrophobic conditions. This suggests, when peptides interact with the membrane they gain

a helix form and will have a disruptive effect on the integrity of the membrane.