Tubules, Rods, and Spirals: Diverse Modes of SepF-FtsZ Assembling.

Z-ring formation by FtsZ, the master assembler of the divisome, is a key step in bacterial cell division. Membrane anchoring of the Z-ring requires the assistance of dedicated Z-ring binding proteins, such as SepF and FtsA. SepF participates in bundling and membrane anchoring of FtsZ in gram-positive bacteria.

BindCraft: one-shot design of functional protein binders.

Protein-protein interactions (PPIs) are at the core of all key biological processes. However, the complexity of the structural features that determine PPIs makes their design challenging. We present BindCraft, an open-source and automated pipeline for protein binder design with experimental success rates of 10-100%.

Biophysical Basis of Paracellular Barrier Modulation by a Pan-Claudin-Binding Molecule.

Claudins are a 27-member protein family that form and fortify specialized cell contacts in endothelium and epithelium called tight junctions. Tight junctions restrict paracellular transport across tissues by forming molecular barriers between cells. Claudin-binding molecules thus hold promise for modulating tight junction permeability to deliver drugs or as therapeutics to treat tight junction-linked disease.

Computational design of soluble and functional membrane protein analogues.

De novo design of complex protein folds using solely computational means remains a substantial challenge. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from G-protein-coupled receptors, are not found in the soluble proteome, and we demonstrate that their structural features can be recapitulated in solution.

SAXS/WAXS data of conformationally flexible ribose binding protein.

Modern artificial intelligence-based protein structure prediction methods, such as Alphafold2, can predict structures of folded proteins with reasonable accuracy. However, Alphafold2 provides a static view of a protein, which does not show the conformational variability of the protein, domain movement in a multi-domain protein, or ligand-induced conformational changes it might undergo in solution. Small-angle X-ay scattering (SAXS) and wide-angle X-ray scattering (WAXS) are solution techniques that can aid in integrative modeling of conformationally flexible proteins, or in validating their predicted ensemble structures.