Computational protein design of ligand binding and catalysis

The vision of custom-made proteins by computation appears closer than ever. Computational methods have advanced rapidly in recent years and proteins have been designed to catalyze new reactions. A number of second-generation enzyme designs analyzed possible bottlenecks and started tackling emergent problems. Detailed experimental analysis combined with structure determination and molecular dynamics simulations as well as design optimization with directed evolution techniques have led to important insights. While ligand recognition seems to be particularly problematic, new approaches focus on this design aspect and promising improvements have been made.