Publication detail

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.

Original Title

Evolutionary Analysis is a Powerful Complement to Energy Calculations Allowing Entropy-Driven Stabilization

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

stability, proteins, dehalogenase, entropy

Authors

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

Released

31. 8. 2018

ISBN

2155-5435

Periodical

ACS Catalysis

Year of study

2018

Number

8

State

United States of America

Pages from

9420

Pages to

9428

Pages count

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 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"
}