title: Computational strategies for the design of new enzymatic functions.
abstract: 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.
authors: Departament de Química Física, Universitat de València, 46100 Burjasot, Spain; Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland.
authors: K
authors: K
authors: Świderek
authors: Departament de Química Física, Universitat de València, 46100 Burjasot, Spain.
authors: I
authors: I
authors: Tuñón
authors: Departament de Química Física i Analítica, Universitat Jaume I, 12071 Castellón, Spain.
authors: V
authors: V
authors: Moliner
authors: Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. Electronic address: bertran@klingon.uab.es.
authors: J
authors: J
authors: Bertran
mesh_terms: D017076:Computer-Aided Design; D015195:Drug Design; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation
chemical_list: D004798:Enzymes; D008667:Metalloproteins
keywords: De novo design; Diels–Alder; Kemp elimination; Molecular dynamics; Protein design; QM/MM; Retro-Aldolase