{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T14:03:56Z","timestamp":1780236236333,"version":"3.54.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Designing functional peptides with specific structural and biochemical properties is critical for applications in protein engineering and therapeutic discovery. However, most peptide design approaches rely on evolutionary or local sequence optimization methods, which are limited when adapting to peptides\u2019 shorter length, high conformational flexibility, and unique physicochemical constraints. While recent structure-based inverse folding models have shown success for proteins, these models often underperform on peptides because sequence recovery alone is not a reliable indicator of stability or foldability in short, flexible backbones. To address this challenge, we introduce InversePep, a generative diffusion model for structure-based peptide inverse folding. InversePep learns the conditional distribution of sequences that can adopt a given backbone conformation, enabling direct generation of peptides tailored to target structural geometries. The framework integrates a geometric graph neural network to encode 3D backbone features with a Transformer-based sequence refinement module that iteratively denoises candidate sequences during diffusion. Trained on a diverse set of peptide backbones sourced from Propedia and SATPdb, InversePep effectively captures structural and biochemical diversity across peptide families. In systematic evaluations on held-out peptide structures and the PepBDB benchmark dataset, InversePep achieves Mean TM-SCORE (0.51), Median TM-SCORE (0.483), Mean RMSD-Simple (1.02), Median RMSD-Simple (0.97), Mean RMSD-Common (3.13), Median RMSD-Common (2.16), outperforming ProteinMPNN, and ESM-IF1 in generating geometry-consistent peptide sequences. In-silico folding analyses confirm that sampled peptides reliably adopt the target conformations. These results highlight InversePep\u2019s capability for designing structurally stable and sequence-diverse peptides, demonstrating its potential in antimicrobial peptide discovery, peptide therapeutics, and molecular probe development.<\/jats:p>","DOI":"10.1093\/bib\/bbag277","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:38:10Z","timestamp":1778585890000},"source":"Crossref","is-referenced-by-count":0,"title":["InversePep: Diffusion-driven structure-based inverse folding for functional peptides"],"prefix":"10.1093","volume":"27","author":[{"given":"Srinivas Kashyap","family":"Chilakamarri","sequence":"first","affiliation":[{"name":"Department of Computer Science and Engineering, Keshav Memorial Engineering College , Uppal, Hyderabad, Telangana 500088 ,","place":["India"]},{"name":"Drugparadigm Research Lab, Uppal , Hyderabad, Telangana 500039 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha Reddy","family":"Kasturi","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Keshav Memorial Engineering College , Uppal, Hyderabad, Telangana 500088 ,","place":["India"]},{"name":"Drugparadigm Research Lab, Uppal , Hyderabad, Telangana 500039 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Pranav Reddy","family":"Yerrabandla","sequence":"additional","affiliation":[{"name":"Drugparadigm Research Lab, Uppal , Hyderabad, Telangana 500039 ,","place":["India"]},{"name":"Department of Computer Science and Engineering, Neil Gogte Institute of Technology , Uppal, Hyderabad, Telangana 500088 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjana","family":"Gogte","sequence":"additional","affiliation":[{"name":"Drugparadigm Research Lab, Uppal , Hyderabad, Telangana 500039 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0991-5003","authenticated-orcid":false,"given":"Vani","family":"Kondaparthi","sequence":"additional","affiliation":[{"name":"Drugparadigm Research Lab, Uppal , Hyderabad, Telangana 500039 ,","place":["India"]},{"name":"Department of Chemistry, Keshav Memorial Engineering College , Uppal, Hyderabad, Telangana 500088 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"2026053109470037600_ref1","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1111\/cbdd.14180","article-title":"Peptide-based diagnostic and therapeutic agents: where we are and where we are heading?","volume":"101","author":"Khalily","year":"2023","journal-title":"Chem Biol Drug 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