Computational Design of Stable and Soluble Biocatalysts
Milos Musil
Hannes Konegger
Jiri Hon
David Bednar
Jiri Damborsky
10.1021/acscatal.8b03613.s001
https://acs.figshare.com/articles/journal_contribution/Computational_Design_of_Stable_and_Soluble_Biocatalysts/7552916
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 cosolvents. 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, and the
number of sequences available for phylogenetic analyses is growing.
In addition, 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.
2018-12-18 00:00:00
phylogenetic analyses
solubility
design optimized protein sequences
Soluble Biocatalysts Natural enzymes
protein stability predictions