Speaker
Description
Membrane-binding peptides hold considerable promise for applications such as antimicrobials, biosensors, and extracellular vesicle purification. However, their successful implementation in biotechnology requires careful consideration of membrane selectivity. The Opi1 peptide has demonstrated a selective affinity for phosphatidic acid–containing membranes, as shown experimentally by Ernst et al. [1]. Luevano-Martínez et al. [2] further reported that the modulation of Opi1-related genes in yeast directly influences the cardiolipin content of membranes. This observation, together with the chemical similarities between phosphatidic acid and cardiolipin, suggests that Opi1 also exhibits notable affinity for cardiolipin, which is found in inner mitochondrial membranes as well as in some bacterial membranes. Nevertheless, only a limited range of bacteria contain substantial amounts of cardiolipin. Thus, peptides with selective affinity for other lipids, such as phosphatidylglycerol or phosphatidylethanolamine, are required to address the natural diversity of membrane compositions [3]. In this study, we use the Opi1 peptide as a reference framework to rationally design peptide derivatives with broader membrane selectivity. Our approach employs advanced computational methodologies for free energy calculations, including alchemical free energy transformations and umbrella sampling. Preliminary results indicate that Opi1 selectivity can be modulated through specific point mutations. The resulting mutants exhibit distinct patterns of selectivity toward human and bacterial membranes.
[1] Ernst, et al. J. Cell Biol. 2018, 217(9), 3109-3126. https://doi.org/10.1083/jcb.201802027
[2] Luévano-Martínez, et al. Fungal Genetics and Biology. 2013, 60, 150-158. https://doi.org/10.1016/j.fgb.2013.03.005
[3] Malanovic, et al. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2020, 1862(8), 183275. https://doi.org/10.1016/j.bbamem.2020.183275
