AutoHMD: Scalable and Accurate Validation of Antibody-Antigen Complexes by Heated Molecular Dynamics.

Heated molecular dynamics (HMD) with AutoHMD accurately discriminates near-native antibody-antigen binding poses, achieving 90% accuracy with a mean iRMSD cutoff of approximately 2.5 Å.

• Why it matters: Accurate structural characterization of antibody-antigen complexes is crucial for immune recognition and therapeutic design, but existing static scoring methods struggle to distinguish near-native conformations due to the dynamic nature of interfaces.
• What they did: The study evaluated HMD as a dynamic validation approach across diverse antibody-antigen complexes, using automated workflows and multiple simulation replicates to assess pose stability under thermal perturbation.
• The result: AutoHMD effectively separates high-quality from incorrect poses by analyzing interface stability, with increased replicates improving classification consistency, supporting its application in structural bioinformatics and biopharmaceutical development.