Designing artificial enzymes by intuition and computation

Abstract

Nature's enzymes are remarkably efficient at catalysing highly specific reactions with extraordinary selectivity. The ability to design enzymes for any desired reaction is a huge challenge. Here, the advances in the development of artificial enzymes are discussed with a particular focus on the computational advances that bring this challenge closer to reality. The rational design of artificial enzymes, either by applying physico–chemical intuition of protein structure and function or with the aid of computational methods, is a promising area of research with the potential to tremendously impact medicine, industrial chemistry and energy production. Designed proteins also provide a powerful platform for dissecting enzyme mechanisms of natural systems. Artificial enzymes have come a long way from simple α-helical peptide catalysts to proteins that facilitate multistep chemical reactions designed by state-of-the-art computational methods. Looking forward, we examine strategies employed by natural enzymes that could be used to improve the speed and selectivity of artificial catalysts.