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@article{1410442,
author = {Jandova, Z. and Trošanová, Zuzana and Weisová, Veronika and Oostenbrink, C. and Hritz, Jozef},
article_location = {Amsterdam, The Netherlands},
article_number = {3},
doi = {http://dx.doi.org/10.1016/j.bbapap.2017.11.012},
keywords = {14-3-3 protein; Protein stability; Molecular dynamics simulation; Differential scanning calorimetry; Free energy calculation; Thermodynamic integration},
language = {eng},
issn = {1570-9639},
journal = {Biochimica et Biophysica Acta - Proteins and Proteomics},
title = {Free energy calculations on the stability of the 14-3-3 zeta protein},
url = {https://www.sciencedirect.com/science/article/pii/S1570963917302807?via%3Dihub},
volume = {1866},
year = {2018}
}
TY - JOUR
ID - 1410442
AU - Jandova, Z. - Trošanová, Zuzana - Weisová, Veronika - Oostenbrink, C. - Hritz, Jozef
PY - 2018
TI - Free energy calculations on the stability of the 14-3-3 zeta protein
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
VL - 1866
IS - 3
SP - 442-450
EP - 442-450
PB - Elsevier
SN - 15709639
KW - 14-3-3 protein
KW - Protein stability
KW - Molecular dynamics simulation
KW - Differential scanning calorimetry
KW - Free energy calculation
KW - Thermodynamic integration
UR - https://www.sciencedirect.com/science/article/pii/S1570963917302807?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S1570963917302807?via%3Dihub
N2 - Mutations of cysteine are often introduced to e.g. avoid formation of non-physiological inter-molecular disulfide bridges in in-vitro experiments, or to maintain specificity in labeling experiments. Alanine or serine is typically preferred, which usually do not alter the overall protein stability, when the original cysteine was surface exposed. However, selecting the optimal mutation for cysteines in the hydrophobic core of the protein is more challenging. In this work, the stability of selected Cys mutants of 14-3-3 zeta was predicted by free-energy calculations and the obtained data were compared with experimentally determined stabilities. Both the computational predictions as well as the experimental validation point at a significant destabilization of mutants C94A and C94S. This destabilization could be attributed to the formation of hydrophobic cavities and a polar solvation of a hydrophilic side chain. A L12E, M78K double mutant was further studied in terms of its reduced dimerization propensity. In contrast to naive expectations, this double mutant did not lead to the formation of strong salt bridges, which was rationalized in terms of a preferred solvation of the ionic species. Again, experiments agreed with the calculations by confirming the monomerization of the double mutants. Overall, the simulation data is in good agreement with experiments and offers additional insight into the stability and dimerization of this important family of regulatory proteins.
ER -
JANDOVA, Z., Zuzana TROŠANOVÁ, Veronika WEISOVÁ, C. OOSTENBRINK and Jozef HRITZ. Free energy calculations on the stability of the 14-3-3 zeta protein. \textit{Biochimica et Biophysica Acta - Proteins and Proteomics}. Amsterdam, The Netherlands: Elsevier, 2018, vol.~1866, No~3, p.~442-450. ISSN~1570-9639. Available from: https://dx.doi.org/10.1016/j.bbapap.2017.11.012.
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