A defined structural unit enables de novo design of small-molecule-binding proteins.

Publication Type:

Journal Article

Source:

Science, Volume 369, Issue 6508, p.1227-1233 (2020)

Abstract:

<p>The de novo design of proteins that bind highly functionalized small molecules represents a great challenge. To enable computational design of binders, we developed a unit of protein structure-a van der Mer (vdM)-that maps the backbone of each amino acid to statistically preferred positions of interacting chemical groups. Using vdMs, we designed six de novo proteins to bind the drug apixaban; two bound with low and submicromolar affinity. X-ray crystallography and mutagenesis confirmed a structure with a precisely designed cavity that forms favorable interactions in the drug-protein complex. vdMs may enable design of functional proteins for applications in sensing, medicine, and catalysis.</p>

PDB: 
6W6X, 6W70
Detector: 
EIGER
Beamline: 
24-ID-E
6W70