Computational Design of Biologically Active Anticancer Peptides and Their Interactions with Heterogeneous POPC/POPS Lipid Membranes

Over the last few decades, anticancer peptides (ACPs) have turned into potential warheads against cancer. Apart from small molecules and monoclonal antibodies, ACPs have been proven to be effective against cancer cells. ACPs are small cationic peptides that selectively bind to the negatively charged cancer cell membrane and kill them by various mechanisms. In the present study, we prepared a random scrambled library of 1200 peptides from the 100 known ACPs and virtually screened them for their anticancer properties. From in silico-predicted ACPs, 27 peptides were prioritized based on their support vector machine (SVM) score. Based on the SVM score and properties such as hydrophobicity, size, overall net charge, secondary structure, and synthetic feasibility, finally, four peptides were synthesized and screened for their biological activities. Cancer cell membrane-deforming potential of two most active peptides, peptide1 and peptide2 was assessed with molecular dynamics simulation. We found that peptide1 remains adsorbed to the membrane surface, while peptide2 has membrane penetration capability. The present study will be helpful in the computational design of ACPs and understanding their interaction with the cancerous cell's membrane.