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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00101752" target="_blank" >RIV/00216224:14310/18:00101752 - isvavai.cz</a>

Alternative codes found

RIV/00159816:_____/18:00069351

Result on the web

<a href="http://dx.doi.org/10.1021/acscatal.8b01677" target="_blank" >http://dx.doi.org/10.1021/acscatal.8b01677</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acscatal.8b01677" target="_blank" >10.1021/acscatal.8b01677</a>

Result language

angličtina

Original language name

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

Original language description

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 tested four different hypotheses to explain the molecular basis of stabilization using structural, biochemical, biophysical, and computational analyses. We demonstrate that stabilization of DhaA by the mutations identified using the phylogenetic analysis is driven by both entropy and enthalpy contributions, in contrast to primarily enthalpy-driven stabilization by mutations designed by the force-field Comprehensive bioinformatics analysis revealed that more than half (53%) of 1 099 evolution-based stabilizing mutations would be evaluated as destabilizing by force-field calculations. Thermodynamic integration considers both folded and unfolded states and can describe the entropic component of stabilization, yet it is not suitable for predictive purposes due to its high computational demands. Altogether, our results strongly suggest that energetic calculations should be complemented by a phylogenetic analysis in protein-stabilization endeavors.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ACS Catalysis

ISSN

2155-5435

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

9420-9428

UT code for WoS article

000447224100051

EID of the result in the Scopus database

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