Institute of Fundamental Technological Research
Polish Academy of Sciences


A. Dujmović

Recent publications
1.  Liu Z., Moreira R.A., Dujmović A., Liu H., Yang B., Poma A.B., Nash M.A., Mapping mechanostable pulling geometries of a therapeutic anticalin/CTLA-4 protein complex, Nano Letters, ISSN: 1530-6984, DOI: 10.1021/acs.nanolett.1c03584, Vol.22, pp.179-187, 2022

We used single-molecule AFM force spectroscopy (AFM-SMFS) in combination with click chemistry to mechanically dissociate anticalin, a non-antibody protein binding scaffold, from its target (CTLA-4), by pulling from eight different anchor residues. We found that pulling on the anticalin from residue 60 or 87 resulted in significantly higher rupture forces and a decrease in koff by 2–3 orders of magnitude over a force range of 50–200 pN. Five of the six internal anchor points gave rise to complexes significantly more stable than N- or C-terminal anchor points, rupturing at up to 250 pN at loading rates of 0.1–10 nN s^–1. Anisotropic network modeling and molecular dynamics simulations helped to explain the geometric dependency of mechanostability. These results demonstrate that optimization of attachment residue position on therapeutic binding scaffolds can provide large improvements in binding strength, allowing for mechanical affinity maturation under shear stress without mutation of binding interface residues.

atomic force microscopy, protein engineering, single-molecule force spectroscopy, mechanical anisotropy, click chemistry, Go̅-Martini model, PCA

Liu Z. - other affiliation
Moreira R.A. - IPPT PAN
Dujmović A. - other affiliation
Liu H. - Imperial College London (GB)
Yang B. - other affiliation
Poma A.B. - IPPT PAN
Nash M.A. - other affiliation

Category A Plus


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