The field of protein design has made remarkable progress over the past decade. Historically,
the low reliability of purely structure-based design methods limited their application, but …

Proteins are increasingly used in basic and applied biomedical research. Many proteins,
however, are only marginally stable and can be expressed in limited amounts, thus …

Substantial improvements in enzyme activity demand multiple mutations at spatially
proximal positions in the active site. Such mutations, however, often exhibit unpredictable …

Mutations in protein active sites can dramatically improve function. The active site, however,
is densely packed and extremely sensitive to mutations. Therefore, some mutations may …

Highlights•Optimization plateaus are common when engineering enzymes for higher
catalytic efficiency.•These plateaus relate to fundamental properties of evolutionary fitness …

Recent years have seen a dramatic improvement in protein-design methodology.
Nevertheless, most methods demand expert intervention, limiting their widespread adoption …

Many natural and designed proteins are only marginally stable limiting their usefulness in
research and applications. Recently, we described an automated structure and sequence …

New enzyme functions often evolve through the recruitment and optimization of latent
promiscuous activities. How do mutations alter the molecular architecture of enzymes to …

The organophosphorus chemical warfare agents were initially synthesized in the 1930's and
are some of the most toxic compounds ever discovered. The standard means of …

Mining of organophosphorous (OPs)-degrading bacterial enzymes in collections of known
bacterial strains and in natural biotopes are important research fields that lead to the …