Ontology highlight
ABSTRACT:
SUBMITTER: Polizzi NF
PROVIDER: S-EPMC7526616 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Polizzi Nicholas F NF DeGrado William F WF
Science (New York, N.Y.) 20200901 6508
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 structu ...[more]