Detail publikačního výsledku

Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization

BEERENS, K.; MAZURENKO, S.; KUNKA, A.; MARQUES, S.; HANSEN, N.; MUSIL, M.; CHALOUPKOVÁ, R.; WATERMAN, J.; BREZOVSKÝ, J.; BEDNÁŘ, D.; PROKOP, Z.; DAMBORSKÝ, J.

Originální název

Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization

Anglický název

Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization

Druh

Článek WoS

Originální abstrakt

Stability is one of the most important characteristics of proteins employed as biocatalysts, biotherapeutics and biomaterials, and the role of computational approaches in modifying protein stability is rapidly expanding. We have recently identified stabilizing mutations in haloalkane dehalogenase DhaA using phylogenetic analysis, but were not able to reproduce the effects of these mutations using force-field calculations. Here we test four different hypotheses to explain the molecular basis of stabilization using structural, biochemical, biophysical and computational analyses. We demonstrate that protein stabilization by these evolution-based mutations is entropy-driven, in contrast to the enthalpy-driven stabilization by mutations derived from force-field calculations. These results suggest that phylogenetic analysis should always be used to complement energetic calculations in protein stabilization endeavors. Furthermore, the insights gained in this work can stimulate the development of new theoretical approaches for the prediction of entropic contributions to protein stability.

Anglický abstrakt

Stability is one of the most important characteristics of proteins employed as biocatalysts, biotherapeutics and biomaterials, and the role of computational approaches in modifying protein stability is rapidly expanding. We have recently identified stabilizing mutations in haloalkane dehalogenase DhaA using phylogenetic analysis, but were not able to reproduce the effects of these mutations using force-field calculations. Here we test four different hypotheses to explain the molecular basis of stabilization using structural, biochemical, biophysical and computational analyses. We demonstrate that protein stabilization by these evolution-based mutations is entropy-driven, in contrast to the enthalpy-driven stabilization by mutations derived from force-field calculations. These results suggest that phylogenetic analysis should always be used to complement energetic calculations in protein stabilization endeavors. Furthermore, the insights gained in this work can stimulate the development of new theoretical approaches for the prediction of entropic contributions to protein stability.

Klíčová slova

stability, proteins, dehalogenase, entropy

Klíčová slova v angličtině

stability, proteins, dehalogenase, entropy

Autoři

BEERENS, K.; MAZURENKO, S.; KUNKA, A.; MARQUES, S.; HANSEN, N.; MUSIL, M.; CHALOUPKOVÁ, R.; WATERMAN, J.; BREZOVSKÝ, J.; BEDNÁŘ, D.; PROKOP, Z.; DAMBORSKÝ, J.

Rok RIV

2019

Vydáno

31.08.2018

ISSN

2155-5435

Periodikum

ACS Catalysis

Svazek

2018

Číslo

8

Stát

Spojené státy americké

Strany od

9420

Strany do

9428

Strany počet

9

URL

https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2018/09/acscatal18b.pdf

BibTex

@article{BUT154996,
  author="BEERENS, K. and MAZURENKO, S. and KUNKA, A. and MARQUES, S. and HANSEN, N. and MUSIL, M. and CHALOUPKOVÁ, R. and WATERMAN, J. and BREZOVSKÝ, J. and BEDNÁŘ, D. and PROKOP, Z. and DAMBORSKÝ, J.",
  title="Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization",
  journal="ACS Catalysis",
  year="2018",
  volume="2018",
  number="8",
  pages="9420--9428",
  doi="10.1021/acscatal.8b01677",
  issn="2155-5435",
  url="https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2018/09/acscatal18b.pdf"
}

Dokumenty

acscatal.8b01677