Exploratory data analysis of physicochemical parameters of natural antimicrobial and anticancer peptides: Unraveling the patterns and trends for the rational design of novel peptides.

B BioImpacts Saini et al., BioImpacts. 2024;14(1):26438 doi: 10.34172/bi.2023.26438 TUOMS TUOMS https://bi.tbzmed.ac.ir/ PRESS PRESS Publish Free ccess Exploratory data analysis of physicochemical parameters of natural antimicrobial and anticancer peptides: Unraveling the patterns and trends for the rational design of novel peptides Sandeep Saini1,2 , Aayushi Rathore3 , Sheetal Sharma1 , Avneet Saini1* ID ID ID ID Department of Biophysics, Panjab University, Sector 25, Chandigarh 160014, India Department of Bioinformatics, Goswami Ganesh Dutta Sanatan Dharma College, Sector 32-C, Chandigarh 160030, India 3 Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Bengaluru 560100, India 1 2 Article Info Article Type: Original Article Article History: Received: 6 May 2022 Revised: 4 Nov. 2022 Accepted: 4 Dec. 2022 ePublished: 20 Aug. 2023 Keywords: Antimicrobial peptide Anticancer peptide Data analysis Rational design Peptide properties Patterns and trends Abstract Introduction: Peptide-based research has attained new avenues in the antibiotics and cancer drug resistance era. The basis of peptide design research lies in playing with or altering physicochemical parameters. Here in this work, we have done exploratory data analysis (EDA) of physicochemical parameters of antimicrobial peptides (AMPs) and anticancer peptides (ACPs), two promising therapeutics for microbial and cancer drug resistance to deduce patterns and trends. Methods: Briefly, we have captured the natural AMPs and ACPs data from the APD3 database. After cleaning the data manually and by CD-HIT web server, further data analysis has been done using Python-based packages, modlAMP and Pandas. We have extracted the descriptive statistics of 10 physicochemical parameters of AMPs and ACPs to build a comprehensive dataset containing all major parameters. The global analysis of datasets has been done using modlAMP to find the initial patterns in global data. The subsets of AMPs and ACPs were curated based on the length of the peptides and were analyzed by Pandas package to deduce the graphical profile of AMPs and ACPs. Results: EDA of AMPs and ACPs shows selectivity in the length and amino acid compositions. The distribution of physicochemical parameters in defined quartile ranges was observed in the descriptive statistical and graphical analysis. The preferred length range of AMPs and ACPs was found to be 21-30 amino acids, whereas few outliers in each parameter were evident after EDA analysis. Conclusion: The derived patterns from natural AMPs and ACPs can be used for the rational design of novel peptides. The statistical and graphical data distribution findings will help in combining the different parameters for potent design of novel AMPs and ACPs. Introduction According to the World Health Organization (WHO), antimicrobial resistance (AMR) and cancer are severe threats to human health.1 Recently, global AMR and use surveillance system (GLASS) reported laboratoryconfirmed AMR cases in 3 106 602 patients in 70 countries in 2019.2 In the era of antibiotic or multidrug resistance (MDR), there is a need to look for alternative and stable treatment options beyond these small molecules.3 Amongst non-communicable diseases, cancer is the leading cause of death that decreases life expectancy in every country globally. According to the international agency for research on cancer (IARC) GLOBOCAN (2020) database statistics, there were an estimated 19.3 million new cancer cases, and 10 million cancer deaths reported worldwide in 2020.4 Traditional anticancer therapeutics involve surgery, radiation therapy, and chemotherapy as the major treatment options for primary tumors to extensive *Corresponding author: Avneet Saini, Email: © 2024 The Author(s). This work is published by BioImpacts as an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited. Saini et al metastases. However, these traditional therapeutic options suffer from serious problems of drug resistance and adverse side-effects; for instance, data from a clinical study of patients suggest that above 80% of cancer patients acquired single or multiple drug resistance.5 Given the rising prevalence of microbial and cancer drug resistance, there is an essential need to look for alternative therapeutics. Therapeutic peptides (THPs) such as antimicrobial peptides (AMPs) and anticancer peptides (ACPs) are being seen as new arsenals in the era of microbial and cancer drug resistance, respectively.6,7 These peptides provide many advantages over traditional therapeutics drugs because of their better safety.8,9 AMPs are short, cationic, amphiphilic molecules of host defense produced by almost all life forms as components of the innate immune response. They display a broad spectrum of antimicrobial activity against Gram-negative, Grampositive bacteria, fungi, viruses, and parasites.10 Besides antimicrobial activity, the immunomodulatory role of AMPs in mammals to stimulate pro or anti-inflammatory response by activating cells of the immune system (macrophages and mast cells) and anticancer or antitumor activities in various cancer cell lines or mice models are well established.11 The potential of AMPs as safe, effective, and highly selective drugs against several different types of cancers can be exploited to design novel ACPs as potential drugs.12 ACPs share most of the characteristics with AMPs, such as both possess high hydrophobicity (H), net positive charge, and fold into a well-defined alpha helix or betasheet structure upon interaction with cell membranes. However, despite sharing common characteristics, there is still enough uncertainty in the physicochemical parameters that determine the activity of some AMPs against cancer cells.13 The current challenges in peptide therapeutics such as low oral bioavailability, sensitivity to host protease, hemolysis and cytotoxicity, and short half-life hinder the development of successful AMPs or ACPs candidate.14,15 Furthermore, a lack of understanding of rational design approaches further increased the snag in therapeutics peptides development.6 Several previous efforts to explore the physicochemical parameters from the datasets of AMPs or ACPs were mainly made during the curation of peptide databases.16-19 Though, these efforts explored a few physicochemical parameters of the peptides but lack sufficient statistical analysis. Furthermore, a combination of synthetic and natural peptide datasets was used in these studies that may have prevented the overall representation of physicochemical parameters of natural peptides. The challenges in AMPs or ACPs development and design can be better solved by understanding the underlying principles of designing natural peptides, as recently stated by Wang.20 Addi (...truncated)