{
  "id": 4355418,
  "title": "A Simple Method to Distinguish Active and Inactive Aptamers by Analyzing the Ruggedness of the Aptamer Free Energy Landscape",
  "url": "https://urgent.news/2026/08/29/a-simple-method-to-distinguish-active-and-inactive-aptamers-by",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.26.747184v1?rss=1"
  },
  "original_language": "en",
  "account": "Aptamers are engineered nucleic acid molecules, generated through variations of the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process. They are known for their high affinity and specificity in molecular recognition. However, SELEX can sometimes produce sequences that show enrichment without displaying binding efficacy, resulting in inactive aptamers. The Ruggedness Composite Index (RCI) is a new measure proposed to differentiate between active and inactive aptamers. RCI takes into account various factors including landscape partitioning, metastable state distribution, non-uniform occupancy, and structure-energy coupling scale. The folding energy landscape topology of secondary structure has been tested in six different datasets to determine if it can distinguish active from inactive aptamers. The findings reveal that active aptamers have lower RCI values, indicating smoother, funnel-like conformational spaces. In contrast, inactive aptamers exhibit higher RCI values, signifying fragmented, high-entropy landscapes. Classical thermodynamic features, like minimum free energy, show limited ability to differentiate active from inactive aptamers. Sequences with enriched but non-monotonic binding affinity and lack of specificity tend to exhibit elevated ruggedness, suggesting that landscape topology can predict non-specific enrichment. These results suggest that folding landscape organization can indeed predict aptamer activity, thereby establishing RCI as a simple, interpretable measure to enhance candidate prioritization in therapeutic aptamer discovery.",
  "summary": "Aptamers are structured nucleic acid ligands capable of high affinity, high specificity molecular recognition generated using variations of the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) process. However, SELEX often produces sequences that enrich yet may lack binding efficacy. We propose a measure called the Ruggedness Composite Index (RCI) along with a method for…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}