Computational strategies for the design of new enzymatic functions

In this contribution, recent developments in the design of biocatalysts are reviewed with particular emphasis in the de novo strategy. Studies based on three different reactions, Kemp elimination, Diels–Alder and Retro-Aldolase, are used to illustrate different success achieved during the last years. Finally, a section is devoted to the particular case of designed metalloenzymes. As a general conclusion, the interplay between new and more sophisticated engineering protocols and computational methods, based on molecular dynamics simulations with Quantum Mechanics/Molecular Mechanics potentials and fully flexible models, seems to constitute the bed rock for present and future successful design strategies.This work was supported by the Spanish Ministerio de Economía y Competitividad for project CTQ2012-36253-C03, Universitat Jaume I – Spain (project P1·1B2014-26), Generalitat Valenciana – Spain (PROMETEOII/2014/022 and ACOMP/2014/277 projects), Polish National Center for Science (NCN) (grant 2011/02/A/ST4/00246, 2012−2017), the Polish Ministry of Science and Higher Education (“Iuventus Plus” program project no. 0478/IP3/2015/73, 2015-2016) and the USA National Institute of Health (ref. NIH R01 GM065368). Authors acknowledge computational resources from the Servei d’Informàtica of Universitat de València on the ‘Tirant’ supercomputer and the Servei d’Informat̀ica of Universitat Jaume I