Publication Details

Evolutionary Analysis is a Powerful Complement to Energy Calculations Allowing Entropy-Driven 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. Evolutionary Analysis is a Powerful Complement to Energy Calculations Allowing Entropy-Driven Stabilization. ACS Catalysis, 2018, vol. 2018, no. 8, p. 9420-9428. ISSN: 2155-5435.
Czech title
Evoloční analýza je komplementárním nástrojem k výpočtům volné energie a dovoluje entropickou stabilizaci
Type
journal article
Language
English
Authors
Beerens Koen (FIT)
Mazurenko Stanislav, Ph.D.
Kunka Antonín, Mgr., Ph.D.
MARQUES, S.
HANSEN, N.
Musil Miloš, Ing., Ph.D. (DIFS)
Chaloupková Radka (FIT)
WATERMAN, J.
Brezovský Jan (FIT)
Bednář David (FIT)
Prokop Zbyněk (FIT)
Damborský Jiří, prof. Mgr., Dr. (UMEL)
URL
Keywords

stability, proteins, dehalogenase, entropy

Abstract

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.

Published
2018
Pages
9420–9428
Journal
ACS Catalysis, vol. 2018, no. 8, ISSN 2155-5435
DOI
10.1021/acscatal.8b01677
UT WoS
000447224100051
EID Scopus
2-s2.0-85053636839
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 is a Powerful Complement to Energy Calculations Allowing Entropy-Driven 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"
}
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