Identification of subtypes of anticancer peptides based on sequential features and physicochemical properties

Abstract

Anticancer peptides (ACPs) are a kind of bioactive peptides which could be used as a novel type of anticancer drug that has several advantages over chemistry-based drug, including high specificity, strong tumor penetration capacity, and low toxicity to normal cells. As the number of experimentally verified bioactive peptides has increased significantly, various of in silico approaches are imperative for investigating the characteristics of ACPs. However, the lack of methods for investigating the differences in physicochemical properties of ACPs. In this study, we compared the N- and C-terminal amino acid composition for each peptide, there are three major subtypes of ACPs that are defined based on the distribution of positively charged residues. For the first time, we were motivated to develop a two-step machine learning model for identification of the subtypes of ACPs, which classify the input data into the corresponding group before applying the classifier. Further, to improve the predictive power, the hybrid feature sets were considered for prediction. Evaluation by five-fold cross-validation showed that the two-step model trained with sequence-based features and physicochemical properties was most effective in discriminating between ACPs and non-ACPs. The two-step model trained with the hybrid features performed well, with a sensitivity of 86.75%, a specificity of 85.75%, an accuracy of 86.08%, and a Matthews Correlation Coefficient value of 0.703. Furthermore, the model also consistently provides the effective performance in independent testing set, with sensitivity of 77.6%, specificity of 94.74%, accuracy of 88.99% and the MCC value reached 0.75. Finally, the two-step model has been implemented as a web-based tool, namely iDACP, which is now freely available at http://mer.hc.mmh.org.tw/iDACP/.

Pseudanabaena galeata CCNP1313—Biological Activity and Peptides Production

“…Generally, they are selective in their interactions with cellular targets, do not accumulate to toxic levels in organs, and can be easily synthesized or/and modified. Their therapeutic potential as anticancer peptides (ACPs) or antiviral peptides (AVPs) has been extensively explored, frequently with the application of computational screening techniques [ 46 , 50 , 51 , 52 , 53 ]. It was found that due to negatively charged components on the surface of the cancer cell, anticancer peptides should contain cationic amino acid residues (Lys or/and Arg) to facilitate the electrostatic interaction with the cell [ 54 ].…”

“…Therefore, in ACPs, Gly, Lys, and Leu were found to be the dominant components. The activity against cancer cells can also be enhanced by the presence of Pro, Phe, and Tyr [ 53 , 55 ]. Hydrophobic residues and their modifications belong to the main components of several known anticancer cyanobacterial peptide-like structures such as dolastatin-10 [ 56 ], apratoxins [ 57 ], cryptophycins [ 58 ], aurilides [ 59 ], and belamide A [ 60 ].…”

Peptides as Potentially Anticarcinogenic Agent from Functional Canned Meat Product with Willow Extract

“…The biological activity of food-derived peptides, including activity against cancer cells, is determined by their structural characteristics, such as amino acid composition, sequence, length, and total charge/hydrophobicity. Most food-derived anticancer peptides contain short amino acid sequences with residues ranging from 3 to 25 [ 29 ] or even longer [ 30 ], although peptides of lower molecular weight seem to have higher cytotoxicity [ 31 ]. In this study, the identified peptide sequences had a chain length of 7–37 amino acids, with the largest portion of fragments having 13–16 amino acids.…”

Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics

“…The activities of ACPs are affected by the composition of amino acids and their structure [ 18 ]. In the reported ACP databases (from ACP-DL, ACPP, ACPred-FL, AntiCP, iACP, CancerPPD, APD3, and SATPdb) [ 98 , 99 , 100 ], positively charged or hydrophobic amino acids (Gly, Ala, Phe, His, Lys, Leu, and Trp) have been highly observed in ACPs, compared to non-ACPs [ 46 , 101 ]. Especially, the positively charged amino acid, Lys, was frequently observed in ACPs, whereas the frequencies of negatively charged amino acids, Asp and Glu, were less than other amino acids in 1390 ACPs database analysis [ 101 ].…”