Abstract: In one embodiment, a method includes accessing a biomolecule representation of a first biomolecule and processing the biomolecule representation by a machine-learning model trained using sequencing time-series data. The sequencing time-series data was obtained from directed evolution of a population of biomolecules over multiple enrichment rounds where the population of biomolecules in each enrichment round was a unique set of biomolecules with respect to each other enrichment round. The sequencing time-series data for each enrichment round comprises a biomolecule frequency of each biomolecule of the population of biomolecules in the respective enrichment round. The training comprises learning inferred fitness scores of the population of biomolecules for each enrichment round by predicting biomolecule frequencies of the population of biomolecules in the respective enrichment round given biomolecule frequencies of the population of biomolecules in prior enrichment rounds.

Abstract: Provided herein are antibacterial compound peptides active against Gram-negative bacteria. In various embodiments, the compounds act by inhibition of BAM A membrane protein. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Abstract: The present disclosure relates to chimeric ABC transporter proteins and methods of screening for molecules that bind to the periplasmic, extracellular, and/or luminal face of an ABC transporter protein using the chimeric ABC transporters. For example, in some embodiments, screening methods involve providing a chimeric ABC transporter in which one or more regions of the periplasmic, extracellular, and/or luminal face of the ABC transporter are substituted with one or more equivalent regions of the periplasmic, extracellular, and/or luminal face of a different ABC transporter and selecting for molecules that bind to the ABC transporter but do not bind to the chimeric ABC transporter. The disclosure also relates to molecules that bind to the periplasmic, extracellular, and/or luminal face of an ABC transporter protein, for example, identified in such screens.

Abstract: Methods, systems, and computer program products are provided for clustering of similar peptides to detect candidates for target binding. In some embodiments, a method provided herein includes receiving sequencing information and quantification information of a plurality of peptides after target-binding selection in a library. The sequencing information includes amino acid sequences of the plurality of peptides, and the quantification information includes a count of copies of each amino acid sequence in the plurality of peptides. The method further includes computing similarity scores for pairs of the plurality of peptides using the sequencing information. The method further includes grouping the plurality of peptides into clusters based on the similarity scores. The method further includes screening the clusters based on quantification information of peptides in each cluster to obtain candidates for target binding over a pre-set threshold.