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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26230%2F18%3APU130688" target="_blank" >RIV/00216305:26230/18:PU130688 - isvavai.cz</a>

Výsledek na webu

<a href="https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2018/09/acscatal18b.pdf" target="_blank" >https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2018/09/acscatal18b.pdf</a>

DOI - Digital Object Identifier

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

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10201 - Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8)

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

ACS Catalysis

ISSN

2155-5435

e-ISSN

—

Svazek periodika

2018

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

9420-9428

Kód UT WoS článku

000447224100051

EID výsledku v databázi Scopus

2-s2.0-85053636839