Improved Methods for Classification, Prediction, and Design of Antimicrobial Peptides

Abstract

Peptides with diverse amino acid sequences, structures and functions are essential players in biological systems. The construction of well-annotated databases not only facilitates effective information management, search and mining, but also lays the foundation for developing and testing new peptide algorithms and machines. The antimicrobial peptide database (APD) is an original construction in terms of both database design and peptide entries. The host defense antimicrobial peptides (AMPs) registered in the APD cover the five kingdoms (bacteria, protists, fungi, plants, and animals) or three domains of life (bacteria, archaea, and eukaryota). This comprehensive database (http://aps.unmc.edu/AP) provides useful information on peptide discovery timeline, nomenclature, classification, glossary, calculation tools, and statistics. The APD enables effective search, prediction, and design of peptides with antibacterial, antiviral, antifungal, antiparasitic, insecticidal, spermicidal, anticancer activities, chemotactic, immune modulation, or anti-oxidative properties. A universal classification scheme is proposed herein to unify innate immunity peptides from a variety of biological sources. As an improvement, the upgraded APD makes predictions based on the database-defined parameter space and provides a list of the sequences most similar to natural AMPs. In addition, the powerful pipeline design of the database search engine laid a solid basis for designing novel antimicrobials to combat resistant superbugs, viruses, fungi or parasites. This comprehensive AMP database is a useful tool for both research and education.

Peptide Antibiotics Developed by Mimicking Natural Antimicrobial Peptides

“…Similarly, Wang et al showed that a small 12 amino acid portion of catelicidin LL-37 showed significant antibacterial activity however replacing Arg by Lys decreased the activity [43]. We also investigated the positioning of positively charged amino acid on the helix by changing the number of Leu which changed the degree of turn from one positively charged amino acid to the other.…”

Differences in Protease Expression of Mutants Bacillus licheniformis F11

“…Ec-AMP1 is a cationic á-helical hairpin structure held together by a pair of nested disulfide bonds [58]. Interestingly, Glycocin F glycopeptide (PDB: 2KUY, 43 a.a. bacteriocin from Lactobacillus plantarum) shows a similar hairpin fold 59 . The Bacillus subtilis strain 168 produces the extremely stable antibiotic sublancin 168, which is a 37-residue peptide with the similar helix-loop-helix structure (entry 2MIJ) 60 62 .…”

Antimicrobial peptides: Coming to the end of antibiotic era, the most promising agents

“…Due to the increasing number of natural, semi-synthetic or synthetic AMPs, there are several databases are exist for today, which manage information and conduct peptide analysis (Wang 2015). As shown in Figure 1, despite their similar general physical properties, AMPs are classified based on the composition of their amino-acid, size and conformational secondary structures into major groups including peptides with β-strands, amphipathic α-helices, loop structure, and extended structures.…”

“…As a result of this interactions, AMPs are taken up by "self-promoted uptake" pathway and they also affect many intracellular mechanisms to toward the bacterial cell death. The explanation both how AMPs bind to and inhibit endotoxins and how they shown the synergistic interactions with conventional antibiotics are existing by this pathway (Steinberg et al 1997;Yeaman and Yount 2003;Wang et al 2015).…”

“…There are many ongoing studies to overcome the disadvantages that limits the potential clinical applications of AMPs. They generally focused on using the unusual amino acids such as D-forms, acetylation or amidation of the terminal regions, increasing the peptide stability against proteases, immobilization of AMPs on solid materials, using the modern drug delivery systems, such as liposome encapsulation or nanoparticles (Seo et al 2012;Wang et al 2015;Mendez-Samperio 2013). Some AMPs in clinical trials for therapeutic usage, are summarized in Table 1. In conclusion, AMPs have attracted attention as alternative antibiotics due to their desirable properties such as potency, rapid and multiple mechanisms of action, broad spectrum activities, and low potential to induce novel resistance mechanisms, make them excellent prospects.…”