Publication Details
Evolutionary Analysis As a Powerful Complement to Energy Calculations for Protein Stabilization
Mazurenko Stanislav, Ph.D.
Kunka Antonín, Mgr., Ph.D.
MARQUES, S.
HANSEN, N.
Musil Miloš, Ing., Ph.D. (DIFS)
Chaloupková Radka
WATERMAN, J.
Brezovský Jan
Bednář David
Prokop Zbyněk
Damborský Jiří, prof. Mgr., Dr. (UMEL)
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.
@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"
}