AI for redesigning molecular biology tools like affinity tags. Here's a short demo testing ESMFold2 to redesign the FLAG affinity tag using the anti-FLAG antibody structure (M2, PDB: 8RMO) as a reference. Target to redesign = FLAG: DYKDDDDK ESMFold2 was also tested in the opposite direction, where a new potential FLAG tag binder was designed. AI agents made this presentation for the demo using ChimeraX and the OpenAI text to speech API.

Also, an alternative potential FLAG tag binder was designed. In this example, ESMFold2 designed a 158-residue binder that recovers the six FLAG tag contacts the M2 Fab makes.

An interesting constraint for theoretical binder design is limiting the amino acids that can be used. In this example, ESMFold2 was tasked with generating potential binders for GLP-1R using only: - 8 amino acids: SALTYGEK - 6 amino acids: YAKLEG - 3 amino acids: LEK The goal for the design was just to place candidate mini-proteins near the GLP-1R extracellular-domain groove where semaglutide/Ozempic contacts. Fun to see the structures that resulted! Codex put together this nice presentation of the results.

AI for genome mining. Many high-value natural compounds are made by enzymes whose genes group into clusters. For many compounds the pathway is not fully elucidated. Finding those genes, and later testing them, helps piece a pathway together. For instance, a gene that is near a known anchor gene becomes a candidate for a missing step, even when the anchor is only an approximate match. As a demo, Claude picked berberine as a target compound, then ran bioinformatic tools across different plant lineages to compare the pathway's gene architecture and flag candidate genes for open steps. Claude also made this short presentation!

Claude searched four plants for gene clusters related to the berberine pathway. This included the berberine bridge enzyme (BBE), the CYP80 and CYP719 P450s, and O-methyltransferases. 1. Chinese goldthread (Coptis chinensis): the canonical berberine/BIA pathway reference 2. Fourstamen stephania (Stephania tetrandra; TCM han fang ji): known for coupled bisbenzylisoquinoline alkaloids like tetrandrine 3. Fish mint (Houttuynia cordata): where Claude found many BBE-like paralogs spread across the genome 4. Amur cork tree (Phellodendron amurense): a published P450 route, used as comparative context Here is an example where Claude found a tandem of three CYP80-like paralogs beside an anchor gene.

AI for structural biology: given the right harness, tools, and compute, your preferred AI agent can tackle tasks such as building a protein structure from a cryo-EM density map. In this case, Claude assembled a structure, compared its reconstruction to the published structure, then used ChimeraX to create these visuals and make this short presentation video.

Claude also compared several tools for building the protein from the cryo-EM density. In this case, Claude used ModelAngelo, CryoAtom, and Cryo2Struct, and then constructed this dashboard to display the results.