[Published online Journal of Computer Chemistry, Japan Vol.24, 83-85, by J-STAGE]
<Title:> Physics-Based Docking Complements AlphaFold-Multimer Based Selection in de novo Binder Design: A HER2 Affibody Case Study
<Author(s):> Masatomo GO, Motoki INOUE, Takefumi YAMASHITA
<Corresponding author E-Mill:> yamashita.takefumi(at)hoshi.ac.jp
<Abstract:> Accurate antigen binder interfaces are critical for de novo campaigns that use AlphaFold-Multimer (AFM) in selection. In the HER2 ZHER2 affibody case, AFM produced correct monomer folds but placed the binder at a non-native site. Inter-chain Predicted Aligned Error indicated low interface confidence for the AFM complexes. By contrast, a physics-based workflow combining ZDOCK, RMSD-based clustering, and HADDOCK refinement recovered near-native interfaces. These observations indicate that physics-based docking may serve as a complementary approach to AFM-based selection.
<Keywords:> De novo binder design, AlphaFold-Multimer, Docking, Affibody, HER2
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0013/_article/-char/ja/
<Title:> Physics-Based Docking Complements AlphaFold-Multimer Based Selection in de novo Binder Design: A HER2 Affibody Case Study
<Author(s):> Masatomo GO, Motoki INOUE, Takefumi YAMASHITA
<Corresponding author E-Mill:> yamashita.takefumi(at)hoshi.ac.jp
<Abstract:> Accurate antigen binder interfaces are critical for de novo campaigns that use AlphaFold-Multimer (AFM) in selection. In the HER2 ZHER2 affibody case, AFM produced correct monomer folds but placed the binder at a non-native site. Inter-chain Predicted Aligned Error indicated low interface confidence for the AFM complexes. By contrast, a physics-based workflow combining ZDOCK, RMSD-based clustering, and HADDOCK refinement recovered near-native interfaces. These observations indicate that physics-based docking may serve as a complementary approach to AFM-based selection.
<Keywords:> De novo binder design, AlphaFold-Multimer, Docking, Affibody, HER2
<URL:> https://www.jstage.jst.go.jp/article/jccj/24/3/24_2025-0013/_article/-char/ja/
