Protein Design

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.