title: Piloting the membranolytic activities of peptides with a self-organizing map.
abstract: Antimicrobial peptides (AMPs) show remarkable selectivity toward lipid membranes and possess promising antibiotic potential. Their modes of action are diverse and not fully understood, and innovative peptide design strategies are needed to generate AMPs with improved properties. We present a de novo peptide design approach that resulted in new AMPs possessing low-nanomolar membranolytic activities. Thermal analysis revealed an entropy-driven mechanism of action. The study demonstrates sustained potential of advanced computational methods for designing peptides with the desired activity.
authors.affiliation: Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093 Zürich (Switzerland).
authors.forename: Yen-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Thelesklaf
authors.forename: Yi Fan
authors.initials: YF
authors.lastname: Lim
authors.forename: Max
authors.initials: M
authors.lastname: Pillong
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Koehler
authors.forename: Petra S
authors.initials: PS
authors.lastname: Dittrich
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D018625:Microscopy, Atomic Force; D013816:Thermodynamics
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: drug discovery; machine learning; membrane interaction; peptide design; vesicles