{"publication":{"abstract":"We observed that ESMFold2 generated designs with higher α-helical content than natural proteins. We wanted to bring their secondary-structure compositions closer to those found in nature, without retraining the model.\n\nWe added a penalty for helix-like geometry that increased β-sheet and loop content across five targets, with lower confidence scores on average. We're sharing the code, predicted structures, and optimization traces for researchers who want to control binder composition or investigate how structural preferences emerge during design. These experiments establish how steering changes computational predictions. Whether the resulting proteins fold and bind their intended targets remains to be tested.","body":"# View the notebook\n\n::::::div{.info-box}\nThe **full pub** is available [here](https://arcadia-science.github.io/esmfold2-secondary-structure-steering/).\n\nThe **source code** to generate it is available in [this GitHub repo](https://github.com/Arcadia-Science/esmfold2-secondary-structure-steering) (DOI: [10.5281/zenodo.23774585](https://doi.org/10.5281/zenodo.23774585)).\n::::::\n\nIn the future, we hope to host [notebook pubs](https://dx.doi.org/10.57844/arcadia-ca21-23bb) directly on our publishing platform. Until that’s possible, we’ll create stubs like this with key metadata like the DOI, author roles, citation information, and an external link to the pub itself.\n","contributors":[{"user_id":4228,"role":"Supervision","first_name":"James R.","last_name":"Golden","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/James-Arcadia-headshot.png","in_byline":1,"priority":1,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4228,"role":"Validation","first_name":"James R.","last_name":"Golden","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/James-Arcadia-headshot.png","in_byline":1,"priority":1,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Conceptualization","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Experimental design","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Formal analysis","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Methodology","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Software","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Visualization","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4229,"role":"Writing","first_name":"Evan","last_name":"Kiefl","avatar":"https://thestacks-01.s3.amazonaws.com/users/avatars/Evan-Arcadia-headshot.png","in_byline":1,"priority":3,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]},{"user_id":4990,"role":"Critical feedback","first_name":"Rahul","last_name":"Khorana","avatar":"avatars/users/user_4990_1783399919090.jpg","in_byline":0,"priority":2,"affiliations":[{"org_id":2,"name":"Arcadia Science","slug":"arcadia-science","ror_id":"052zd4v68","avatar":"avatars/orgs/org_2_1766013565.jpg"}]}],"created_at":"2026-10-29T21:51:19.667Z","doi":"10.57844/arcadia-x722-5614","version_doi":null,"feedback_form_embed_src":"https://publishing-tools.arcadiascience.com/typeform/AacF8YKM?pub_name=rec7BkfNRi3eY4UbF","id":194,"license":"CC BY","linked_assets":[{"type":"Code","url":"https://github.com/Arcadia-Science/esmfold2-secondary-structure-steering","name":""},{"type":"Data","url":"https://doi.org/10.5281/zenodo.23542792","name":""}],"mediaAssets":[],"orgs":[{"org_id_int":2,"priority":1,"slug":"arcadia-science","name":"Arcadia Science","avatar":"avatars/orgs/org_2_1766013565.jpg"}],"pdf_url":null,"publisher":"The Stacks","references":[],"slug":"result-esmfold2-secondary-structure-steering","social_posts_count":null,"social_posts_embed_src":"https://publishing-tools.arcadiascience.com/twitter/450818396588090652","state":"PUBLISHED","subtitle":"We added a helix penalty that shifted ESMFold2 binder designs toward β-sheets across five targets. The shift began early in optimization and increased the number passing a sheet-content and confidence screen, despite lower average confidence.","tags":["Result","Feedback requested"],"title":"Steering secondary structure in ESMFold2 binder design","version_desc":null,"version_number":1,"versions":[{"id":529,"version_number":1,"version_desc":null,"doi":null,"created_at":"2026-10-29T21:51:19.667Z"}]}}