Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.01.364091v1?rss=1 Authors: Chen, C. H., Starr, C. G., Guha, S., Wimley, W. C., Ulmschneider, M. B., Ulmschneider, J. Abstract: The use of designed antimicrobial peptides as drugs has been impeded by the absence of simple sequence-structure-function relationships and design rules. We demonstrate that the combination of high-throughput library screening with atomistic computer simulations can successfully address this challenge by tuning a previously developed general pore forming peptide into a selective pore former for different lipid types. A library of 2,916 peptides was designed based on the LDKA template. The library peptides were synthesized and screened using a high-throughput orthogonal vesicle leakage assay. Nine different LDKA variants that have unique activity were selected, sequenced, synthesized, and characterized. Despite the minor sequence changes, each of these peptides has unique functional properties, forming either small or large pores and being selective for either neutral or anionic lipid bilayers. Predicting the propensity to aggregate and assemble in a given environment from sequence alone holds the key to functional prediction of membrane permeabilization. Copy rights belong to original authors. Visit the link for more info