Detail publikace

Computational Design of Stable and Soluble Biocatalysts

MUSIL, M. KONEGGER, H. HON, J. BEDNÁŘ, D. DAMBORSKÝ, J.

Originální název

Computational Design of Stable and Soluble Biocatalysts

Typ

článek v časopise ve Web of Science, Jimp

Jazyk

angličtina

Originální abstrakt

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.

Klíčová slova

Aggregation,Computational Design,Force Field,Expressibility,Machine Learning,Phylogenetic Analysis,Enzyme Stability,Enzyme Solubility

Autoři

MUSIL, M.; KONEGGER, H.; HON, J.; BEDNÁŘ, D.; DAMBORSKÝ, J.

Vydáno

1. 2. 2019

ISSN

2155-5435

Periodikum

ACS Catalysis

Ročník

9

Číslo

2

Stát

Spojené státy americké

Strany od

1033

Strany do

1054

Strany počet

22

URL

https://pubs.acs.org/doi/10.1021/acscatal.8b03613

BibTex

@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"
}