Publication Details

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

BEERENS Koen, MAZURENKO Stanislav, KUNKA Antonín, MARQUES Sergio M., HANSEN Niels, MUSIL Miloš, CHALOUPKOVÁ Radka, WATERMAN Jitka, BREZOVSKÝ Jan, BEDNÁŘ David, PROKOP Zbyněk and DAMBORSKÝ Jiří. Evolutionary Analysis is a Powerful Complement to Energy Calculations Allowing Entropy-Driven Stabilization. ACS Catalysis, vol. 2018, no. 8, pp. 9420-9428. ISSN 2155-5435. Available from:
Czech title
Evoloční analýza je komplementárním nástrojem k výpočtům volné energie a dovoluje entropickou stabilizaci
journal article
Beerens Koen (UGENT)
Mazurenko Stanislav, Ph.D. (LL)
Kunka Antonín, Mgr., Ph.D. (LL)
Marques Sergio M. (LL)
Hansen Niels (AUD)
Musil Miloš, Ing., Ph.D. (DIFS FIT BUT)
Chaloupková Radka, Mgr., Ph.D. (LL)
Waterman Jitka (DLS)
Brezovský Jan, Mgr., Ph.D. (LL)
Bednář David, Mgr. (LL)
Prokop Zbyněk, doc. RnDr., Ph.D. (LL)
Damborský Jiří, prof. Mgr., Dr. (LL)

stability, proteins, dehalogenase, entropy


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.

ACS Catalysis, vol. 2018, no. 8, ISSN 2155-5435
American Chemical Society
EID Scopus
   author = "Koen Beerens and Stanislav Mazurenko and Anton\'{i}n Kunka and M. Sergio Marques and Niels Hansen and Milo\v{s} Musil and Radka Chaloupkov\'{a} and Jitka Waterman and Jan Brezovsk\'{y} and David Bedn\'{a}\v{r} and Zbyn\v{e}k Prokop and Ji\v{r}\'{i} Damborsk\'{y}",
   title = "Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization",
   pages = "9420--9428",
   journal = "ACS Catalysis",
   volume = 2018,
   number = 8,
   year = 2018,
   ISSN = "2155-5435",
   doi = "10.1021/acscatal.8b01677",
   language = "english",
   url = ""
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