Publication Details
Computational Design of Stable and Soluble Biocatalysts
Konegger Hannes
Hon Jiří, Ing., Ph.D.
Bednář David
Damborský Jiří, prof. Mgr., Dr. (UMEL)
Aggregation,Computational Design,Force Field,Expressibility,Machine
Learning,Phylogenetic Analysis,Enzyme Stability,Enzyme Solubility
Natural enzymes are delicate biomolecules possessing only marginal thermodynamic
stability. Poorly stable, misfolded, and aggregated proteins lead to huge
economic losses in the biotechnology and biopharmaceutical industries.
Consequently, there is a need to design optimized protein sequences that maximize
stability, solubility, and activity over a wide range of temperatures and pH
values, in buffers of different composition, and in the presence of organic
co-solvents. This has created great interest in using computational methods to
enhance biocatalysts robustness and solubility. Suitable methods include (i)
energy calculations, (ii) machine learning, (iii) phylogenetic analyses and (iv)
combinations of these approaches. We have witnessed impressive progress in the
design of stable enzymes over the last two decades, but predictions of protein
solubility and expressibility are scarce. Stabilizing mutations can be predicted
accurately using available force fields, the number of sequences available for
phylogenetic analyses is growing, and complex computational workflows are being
implemented in intuitive web tools, enhancing the quality of protein stability
predictions. Conversely, solubility predictors are limited by the lack of robust
and balanced experimental data, an inadequate understanding of fundamental
principles of protein aggregation, and a dearth of structural information on
folding intermediates. Here we summarize recent progress in the development of
computational tools for predicting protein stability and solubility, critically
assess their strengths and weaknesses, and identify apparent gaps in data and
knowledge. We also present perspectives on the computational design of stable and
soluble biocatalysts.
@article{BUT155120,
author="Miloš {Musil} and Hannes {Konegger} and Jiří {Hon} and David {Bednář} and Jiří {Damborský}",
title="Computational Design of Stable and Soluble Biocatalysts",
journal="ACS Catalysis",
year="2019",
volume="9",
number="2",
pages="1033--1054",
doi="10.1021/acscatal.8b03613",
issn="2155-5435",
url="https://pubs.acs.org/doi/10.1021/acscatal.8b03613"
}