title: Redesign of water networks for efficient biocatalysis.
abstract: Herein we highlight recent findings on the importance of water networks in proteins, and their redesign and reconfiguration as a new engineering strategy to generate enzymes with modulated binding affinity and improved catalytic versatility. Traditionally, enzyme engineering and drug design have focused on tailoring direct and favorable interactions between protein surfaces and ligands/transition states to achieve stronger binding, or an accelerated manufacturing of medicines, biofuels, fine chemicals and materials. In contrast, the opportunity to relocate water molecules in solvated binding pockets by protein design to improve overall energetics remains essentially unexplored, and fundamental understanding of the elusive processes involved is poor. Rewiring water networks in protein interiors impacts binding affinity, catalysis and the thermodynamic signature of biochemical processes through dynamic mechanisms, and thus has great potential to enhance binding specificity, accelerate catalysis and provide new reaction mechanisms and chemistry, that were not yet explored in nature.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fink
authors.affiliation: School of Chemical Science and Engineering, Division of Applied Physical Chemistry, KTH Royal Institute of Technology, 100 44 Stockholm, Sweden; Science for Life Laboratory, KTH Royal Institute of Technology, 171 21 Stockholm, Sweden. Electronic address: per-olof.syren@biotech.kth.se.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Syrén
mesh_terms: D055162:Biocatalysis; D019277:Entropy; D015202:Protein Engineering / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014867:Water
chemical_list: D011506:Proteins; D014867:Water