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MINI REVIEW article

Front. Pharmacol.

Sec. Pharmacology of Ion Channels and Channelopathies

This article is part of the Research TopicAdvanced Methodologies For Studying Function And Therapeutic Modulation of Ion Channels and Transporter ProteinsView all 6 articles

Antibody-Enabled Structural Biology and AI-Driven Antibody Design

Provisionally accepted
  • 1Independent Researcher, Framingham, MA, United States
  • 2Independent Researcher, Rockville, United States
  • 3Meso Scale Diagnostics LLC, Rockville, United States

The final, formatted version of the article will be published soon.

Abstract Membrane proteins govern essential cellular processes, including ion transport, signal transduction, and molecular recognition, and collectively represent more than half of all current therapeutic targets. Yet their structural characterization remains challenging due to intrinsic instability, amphipathic surfaces, and conformational heterogeneity. Over the past decade, antibody-based approaches, spanning full-length immunoglobulins, antigen-binding fragments (Fabs), nanobodies, and engineered scaffolds such as designed ankyrin repeat proteins (DARPins), have transformed structural biology by stabilizing dynamic states, augmenting molecular weight for cryo-electron microscopy (cryo-EM), and enabling visualization of previously inaccessible complexes. In parallel, advances in artificial intelligence (AI) and machine learning have begun to enhance predictive modeling, accelerate structure determination, and guide rational design of protein-ligand and antibody–antigen interactions. This review examines how antibody engineering and AI-driven computation together are reshaping the landscape of structural biology and therapeutic discovery.

Keywords: antigen-binding fragments (Fabs) , artificial intelligence, cryo-EM, Designed ankyrin repeat proteins (DARPins), GPCR, membrane protein, nanobodies, Structural Biology

Received: 22 Dec 2025; Accepted: 12 Feb 2026.

Copyright: © 2026 Ashraf and Erramilli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Khuram U. Ashraf
Satchal K. Erramilli

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