{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:59:34Z","timestamp":1763553574705,"version":"3.45.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Artif. Intell."],"abstract":"<jats:p>\n                    Generative artificial intelligence is transforming de novo biomolecular design, yet developing models that reliably generate functional, target-specific peptides remains a significant challenge. Here, we introduce and validate a novel two-stage Bidirectional Long Short-Term Memory (BiLSTM) framework for the generative design of short, functional peptides. Our AI pipeline is trained on full-length proteins annotated with specific Gene Ontology (GO) terms related to amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\u03b2) interaction and is fine-tuned on experimentally validated peptide fragments to capture local functional motifs within a global protein context. As a proof-of-concept, we applied this framework to generate peptides targeting A\u03b242, a key pathological agent in Alzheimer\u2019s disease. From 1,000 AI-generated sequences, 25 candidates were shortlisted using biophysical filters (GRAVY, instability index, Shannon entropy), and 11 were prioritized via sequence similarity analysis, designated as AI-Designed Novel Peptides (ADNP1-ADNP11). Structural modeling (AlphaFold2) and docking (pyDockWEB) against A\u03b242 identified ADNP7 as the top candidate, exhibiting a highly favorable docking score (\u221263.33 kcal\/mol), with interactions localized to A\u03b2\u2019s aggregation-prone regions. All-atom molecular dynamics simulations (20 ns) confirmed complex stability, and MM\/PBSA analysis yielded a strong binding free energy (\u221250.6 kcal\/mol), driven primarily by hydrophobic and aromatic interactions involving PHE12 and TRP50 in ADNP7. This work demonstrates that our fine-tuned BiLSTM architecture can successfully generate novel, stable peptide sequences with high predicted binding affinity for a therapeutically relevant target. While the training data included proteins associated with A\u03b2 clearance (GO:0097242), only binding interactions were computationally validated; clearance potential remains a hypothesis for future experimental testing. This study establishes a generalizable, AI-driven pipeline for functional peptide design, with broad applicability across therapeutic discovery and synthetic biology.\n                  <\/jats:p>","DOI":"10.3389\/frai.2025.1709505","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:56:25Z","timestamp":1763553385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Designing novel peptides with amyloid-\u03b2 binding and clearance potential using BiLSTM and molecular dynamics"],"prefix":"10.3389","volume":"8","author":[{"given":"Vinod Kumar","family":"Yata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Om Pritam","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarmani","family":"Dansana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishikta","family":"Gadtya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biswa Ranjan","family":"Meher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarad Pawar Naik","family":"Bukke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narasaiah","family":"Kolliputi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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