Computational protein design is the core thrust of the Bystroff lab.
We use an approach called "leave-one-out" biosensor design, in which a sequence is designed to fit
a protein of known structure with a segment omitted (the target site). The sequence of the omitted
segment is replaced by the target sequence for sensing. Then protein design builds
a complementary shape into the pocket of the omitted segment, creating a binding site.
The computational design approach is based on the Dead End Elimination algorithm, with
our own modifications. Initial experimental studies have shown that leave-one-out
design works and gives us biosensor with sub-micromolar affinity for the target sequence.
A peptide biosensor based on green fluorescent protein (GFP).
click for a closer look