Structural highlights
Publication Abstract from PubMed
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.
A defined structural unit enables de novo design of small-molecule-binding proteins.,Polizzi NF, DeGrado WF Science. 2020 Sep 4;369(6508):1227-1233. doi: 10.1126/science.abb8330. PMID:32883865[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Polizzi NF, DeGrado WF. A defined structural unit enables de novo design of small-molecule-binding proteins. Science. 2020 Sep 4;369(6508):1227-1233. doi: 10.1126/science.abb8330. PMID:32883865 doi:http://dx.doi.org/10.1126/science.abb8330
