Encodings and models for antimicrobial peptide classification for multi-resistant pathogens

Abstract

Antimicrobial peptides (AMPs) are part of the inherent immune system. In fact, they occur in almost all organisms including, e.g., plants, animals, and humans. Remarkably, they show effectivity also against multi-resistant pathogens with a high selectivity. This is especially crucial in times, where society is faced with the major threat of an ever-increasing amount of antibiotic resistant microbes. In addition, AMPs can also exhibit antitumor and antiviral effects, thus a variety of scientific studies dealt with the prediction of active peptides in recent years. Due to their potential, even the pharmaceutical industry is keen on discovering and developing novel AMPs. However, AMPs are difficult to verify in vitro, hence researchers conduct sequence similarity experiments against known, active peptides. Unfortunately, this approach is very time-consuming and limits potential candidates to sequences with a high similarity to known AMPs. Machine learning methods offer the opportunity to explore the huge space of sequence variations in a timely manner. These algorithms have, in principal, paved the way for an automated discovery of AMPs. However, machine learning models require a numerical input, thus an informative encoding is very important. Unfortunately, developing an appropriate encoding is a major challenge, which has not been entirely solved so far. For this reason, the development of novel amino acid encodings is established as a stand-alone research branch. The present review introduces state-of-the-art encodings of amino acids as well as their properties in sequence and structure based aggregation. Moreover, albeit a wellchosen encoding is essential, performant classifiers are required, which is reflected by a tendency towards specifically designed models in the literature. Furthermore, we introduce these models with a particular focus on encodings derived from support vector machines and deep learning approaches. Albeit a strong focus has been set on AMP predictions, not all of the mentioned encodings have been elaborated as part of antimicrobial research studies, but rather as general protein or peptide representations.

Assessment of in vitro bioactivities of Pis v 1 (2S albumin) and Pis v 2.0101 (11S globulin) proteins derived from pistachio (Pistacia vera L.)

“…Recently, many viral diseases were treated with a combination of synthetic drugs which improve sustained virological response, but also produce adverse side effects including anemia and gastrointestinal symptoms [14]. In addition, antimicrobial proteins can exhibit antitumor and antiviral effects [27]. It has been reported that two allergens of pistachio inhibited several group B Coxsackie viruses.…”

“…Proteins have been regarded as candidates for treatment of cancer or inflammatory diseases and were shown to trigger apoptosis and prevent angiogenesis. Anticancer proteins are able to stimulate host defense system cells and tissues via direct and indirect interaction with host's genes and proteins [27].…”

Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

“…AMPs are either of natural origin, such as those isolated from insects [ 378 ], or designed [ 379 ] either by computer [ 380 ], following QASR-studies on the designer molecule [ 381 ] or after synthetic (experimental) precursor manipulation [ 382 ]. The natural AMPs are part of the inherent immune system in all known taxa but Archaea, [ 380 , 383 ], and many of them were found to be effective against multiresistant pathogens, usually, with high selectivity [ 383 ] Encodings and models for antimicrobial peptide classification for multi-resistant pathogens have then been developed, [ 383 ]. Based on conclusions drawn from QSAR and in vitro bioassays the putative promising chemical derivatives will then be structurally optimized [ 384 ].…”

“…Synthetic candidate derivatives including those substituted with unusual amino acids [ 385 ] share unique features such as serum stability, lack of side effects, and owing intracellular target specificity. The discovery of a new natural AMP molecule is usually followed by quantitative structure/activity (QSAR) studies [ 381 ], and then the design and optimization of analog molecules [ 379 , 380 , 381 , 382 , 383 , 384 , 385 ] then the best ones finally will chemically be synthesized. The most promising molecular family is the proline-arginine rich peptide (PrAMP) [ 386 ].…”

Comparison of the structure and function of a chimeric peptide modified titanium surface

“…[21][22][23] Antimicrobial peptides, according to their source, can be categorized into microbial, animal and plant origin. 24,25 Because of its endogenous and powerful antimicrobial activity, the human betadefensin-3 (hBD-3) is being studied as a multipurpose antimicrobial peptide. 26,27 The known fragments of hBD-3 have anti-inammatory and membrane permeating properties.…”