Abstract
Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from -proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub.
Highlights
There are many health care issues that challenge the welfare of humankind; among them, cancer and antimicrobial resistance are of ever-growing concern
anticancer peptides (ACPs) and antimicrobial peptides (AMPs) are generally considered to be similar in terms of properties and the mode of action, the differences in their amino acid composition are significant enough (Supplementary Tables S1–S3) to find informative motifs that characterize them and non-ACPs/non-AMPs, thereby training an effective model for predicting ACPs
The positive charge, hydrophobicity and amphipathicity are responsible for AMP and ACP selectivity towards microbial membranes and, in the case of ACPs, for targeting the cancer plasma and mitochondrial membranes
Summary
There are many health care issues that challenge the welfare of humankind; among them, cancer and antimicrobial resistance are of ever-growing concern. According to the World Health Organization, cancer is a leading cause of death globally, responsible for about 9.6 million deaths in 2018 [1], and antimicrobial resistance threatens our ability to treat an increasing number of infectious diseases, with a death toll of tens of thousands of people in Europe and the United States [2,3]. Both these challenges could be approached with cationic peptides, antimicrobial peptides (AMPs) and anticancer peptides (ACPs), respectively. AMPs target microbial membranes, especially bacterial envelopes, but ACPs, apart from their antimicrobial activity, exhibit anticancer properties due to slightly different amino acid composition (for details, see [13] and Section 3.1)
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