Redesign of water networks for efficient biocatalysis

• Published in: Current opinion in chemical biology Vol. 37; pp. 107 - 114
• Main Authors: Fink, Michael J, Syrén, Per-Olof
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2017
• Subjects: Biocatalysis; Entropy; Protein Engineering - methods; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Substrate Specificity; Water
• ISSN: 1367-5931; 1879-0402; 1879-0402
• DOI: 10.1016/j.cbpa.2017.02.013

[Display omitted] •Dynamics of water expand the amino acid alphabet.•Redesign of water networks can accelerate the evolution of new biocatalytic functions.•Water networks contribute to enthalpy–entropy compensation.•Interfacial water impacts enzyme specificity, activity and thermodynamics. 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.