TY - JOUR AU - Ragonis-Bachar, Peleg AU - Axel, Gabriel AU - Blau, Shahar AU - Ben-Tal, Nir AU - Kolodny, Rachel AU - Landau, Meytal TI - What can AlphaFold do for antimicrobial amyloids? JO - Proteins VL - 92 IS - 2 SN - 0887-3585 CY - New York, NY PB - Wiley-Liss M1 - PUBDB-2023-06067 SP - 265 - 281 PY - 2023 AB - Amyloids, protein, and peptide assemblies in various organisms are crucial in physiological and pathological processes. Their intricate structures, however, present significant challenges, limiting our understanding of their functions, regulatory mechanisms, and potential applications in biomedicine and technology. This study evaluated the AlphaFold2 ColabFold method's structure predictions for antimicrobial amyloids, using eight antimicrobial peptides (AMPs), including those with experimentally determined structures and AMPs known for their distinct amyloidogenic morphological features. Additionally, two well-known human amyloids, amyloid-β and islet amyloid polypeptide, were included in the analysis due to their disease relevance, short sequences, and antimicrobial properties. Amyloids typically exhibit tightly mated β-strand sheets forming a cross-β configuration. However, certain amphipathic α-helical subunits can also form amyloid fibrils adopting a cross-α structure. Some AMPs in the study exhibited a combination of cross-α and cross-β amyloid fibrils, adding complexity to structure prediction. The results showed that the AlphaFold2 ColabFold models favored α-helical structures in the tested amyloids, successfully predicting the presence of α-helical mated sheets and a hydrophobic core resembling the cross-α configuration. This implies that the AI-based algorithms prefer assemblies of the monomeric state, which was frequently predicted as helical, or capture an α-helical membrane-active form of toxic peptides, which is triggered upon interaction with lipid membranes. LB - PUB:(DE-HGF)16 C6 - 37855235 UR - <Go to ISI:>//WOS:001086319000001 DO - DOI:10.1002/prot.26618 UR - https://bib-pubdb1.desy.de/record/596134 ER -