title: Sparse Neural Network Models of Antimicrobial Peptide-Activity Relationships.
abstract: We present an adaptive neural network model for chemical data classification. The method uses an evolutionary algorithm for optimizing the network structure by seeking sparsely connected architectures. The number of hidden layers, the number of neurons in each layer and their connectivity are free variables of the system. We used the method for predicting antimicrobial peptide activity from the amino acid sequence. Visualization of the evolved sparse network structures suggested a high charge density and a low aggregation potential in solution as beneficial for antimicrobial activity. However, different training data sets and peptide representations resulted in greatly varying network structures. Overall, the sparse network models turned out to be less accurate than fully-connected networks. In a prospective application, we synthesized and tested 10 de novo generated peptides that were predicted to either possess antimicrobial activity, or to be inactive. Two of the predicted antibacterial peptides showed cosiderable bacteriostatic effects against both Staphylococcus aureus and Escherichia coli. None of the predicted inactive peptides possessed antibacterial properties. Molecular dynamics simulations of selected peptide structures in water and TFE suggest a pronounced peptide helicity in a hydrophobic environment. The results of this study underscore the applicability of neural networks for guiding the computer-assisted design of new peptides with desired properties.
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Müller
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.
authors.forename: Aral C
authors.initials: AC
authors.lastname: Kaymaz
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.
authors.forename: Gisela
authors.initials: G
authors.lastname: Gabernet
authors.affiliation: Department of Molecular Biology, Division of Microbiology, Paris Lodron, University of Salzburg, Billrothstr. 11, A-5020, Salzburg, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Posselt
authors.affiliation: Department of Molecular Biology, Division of Microbiology, Paris Lodron, University of Salzburg, Billrothstr. 11, A-5020, Salzburg, Austria.
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017076:Computer-Aided Design; D004926:Escherichia coli / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests / Q000379:methods; D056004:Molecular Dynamics Simulation; D016571:Neural Networks, Computer; D011446:Prospective Studies; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: antibiotic; deep learning; evolutionary algorithm; machine learning; molecular dynamics simulation; structure-activity relationship