Role of conformational dynamics in the evolution of novel enzyme function

Chemical Communications : Chem Comm
Miguel A Maria-SolanoSílvia Osuna

Abstract

The free energy landscape concept that describes enzymes as an ensemble of differently populated conformational sub-states in dynamic equilibrium is key for evaluating enzyme activity, enantioselectivity, and specificity. Mutations introduced in the enzyme sequence can alter the populations of the pre-existing conformational states, thus strongly modifying the enzyme ability to accommodate alternative substrates, revert its enantiopreferences, and even increase the activity for some residual promiscuous reactions. In this feature article, we present an overview of the current experimental and computational strategies to explore the conformational free energy landscape of enzymes. We provide a series of recent publications that highlight the key role of conformational dynamics for the enzyme evolution towards new functions and substrates, and provide some perspectives on how conformational dynamism should be considered in future computational enzyme design protocols.

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Citations

Jan 3, 2019·Angewandte Chemie·Christian Curado-CarballadaSílvia Osuna
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Methods Mentioned

BETA
X-ray
PCA
protein folding

Software Mentioned

Metadynamics
NAMD
AceMD
POVME
CASTing
Map
Rosetta
DynaComm
tICA
OpenMM

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