Enabling the Discovery and Virtual Screening of Potent and Safe Antimicrobial Peptides. Simultaneous Prediction of Antibacterial Activity and Cytotoxicity

Abstract

Antimicrobial peptides (AMPs) represent promising alternatives to fight against bacterial pathogens. However, cellular toxicity remains one of the main concerns in the early development of peptide-based drugs. This work introduces the first multitasking (mtk) computational model focused on performing simultaneous predictions of antibacterial activities, and cytotoxicities of peptides. The model was created from a data set containing 3592 cases, and it displayed accuracy higher than 96% for classifying/predicting peptides in both training and prediction (test) sets. The technique known as alanine scanning was computationally applied to illustrate the calculation of the quantitative contributions of the amino acids (in their respective positions of the sequence) to the biological effects of a defined peptide. A small library formed by 10 peptides was generated, where peptides were designed by considering the interpretations of the different descriptors in the mtk-computational model. All the peptides were predicted to exhibit high antibacterial activities against multiple bacterial strains, and low cytotoxicity against various cell types. The present mtk-computational model can be considered a very useful tool to support high throughput research for the discovery of potent and safe AMPs.

ProtDCal‐Suite: A web server for the numerical codification and functional analysis of proteins

“…The capability of ProtDCal to generate useful features was assessed in several studies developing novel machine learning-based tools. [9][10][11][12][13][14][15][16][17][18][19] Here, we present web interfaces for predicting the interaction likelihood of protein-protein and protein-peptide pairs (PPI-Detect), for identifying enzymes from amino acid sequences or 3D structures (Enzyme Identifier), and for predicting N-glycosylation sites in peptides and proteins (Pred-NGlyco).…”

“…ProtDCal's features have been used to develop predictors for protein analysis. 9,[14][15][16][17]19,20 In ProtDCal-Suite we provide, for the first time, web access to some of these tools.…”

“…In this context, ProtDCal is a software package that transforms protein sequences or 3D‐structures into general‐purpose numerical descriptors, accounting for both global and local information . Due to its complementary performance with respect to other well‐established tools in the field like PROFEAT and PseAcc (later extended to Pse‐in‐one), ProtDCal has been used in a number of studies . Notable among them are the modeling of posttranslational modifications, the prediction of protein enzymatic function, the prediction of antimicrobial activity in peptides, the determination of residues critical for protein function, and the prediction of stability changes upon mutations .…”

“…5 Due to its complementary performance with respect to other well-established tools in the field like PROF-EAT 6 and PseAcc 7 (later extended to Pse-in-one 8 ), ProtDCal has been used in a number of studies. [9][10][11][12][13][14][15][16][17][18][19] Notable among them are the modeling of posttranslational modifications, 14 the prediction of protein enzymatic function, 15 the prediction of antimicrobial activity in peptides, 16 the determination of residues critical for protein function, 17 and the prediction of stability changes upon mutations. 18 Very recently, ProtDCal was enhanced with a procedure for encoding protein pairs, which allows targeting the protein-protein interaction identification problem.…”

FRAMA 1.0: Framework for Moving Average Operators Calculation in Data Analysis

“…(2-7). Speck-Planche and Cordeiro have also used this kind of models in multiple problems (8)(9)(10)(11). In this work, we develop a desktop application that allows applying mathematical and statistical calculations in batches, on input and output variables selected by the user.…”