Computational protein design of ligand binding and catalysis

Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently

“…459 Notable examples include a metalloenzyme for organophosphate hydrolysis, 460,461 aldolase 462,463 and others. 464–468 Theozymes 469–472 (theoretical catalysts, constructed by computing the optimal geometry for transition state stabilization by model functional) groups represent another approach.…”

Synthetic protein switches: design principles and applications

“…Overall, this should greatly facilitate the challenging task of constructing protein-based switches, which has so far proven intractable to computational design methods [10,11] (Box 1).…”

“…Notably, affordable DNA synthesis in association with the abundant availability of sequenced genomes from diverse phyla has yielded an unlimited repertoire of biological parts from which binders, linkers, and enzymes can be sourced to construct recombinant sensors, transducers, and actuators. This is complemented by powerful computational design algorithms that, in some cases, could predict protein structures to angstrom resolution, engineer enzyme active site de novo, and introduce protein-and small molecule-binding sites [10,11].…”

Computational protein design for given backbone: recent progresses in general method-related aspects

“…the energy function) with respect to the amino acid sequence ( Figure 3). The same approach is employed to design protein-protein [7] or protein-small molecule binding interfaces [8]. Through CPD, the number of fully automatically designed proteins that form thermodynamically stable and well-defined structures have been increasing continuously.…”