Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments
In the current work we study, via molecular simulations and experiments, the folding and stability of proteins from the tertiary motif of 4-α-helical bundles, a recurrent motif consisting of four amphipathic α-helices packed in a parallel or antiparallel fashion. The focus is on the role of the loop...
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2021-05-01
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author | Maria Arnittali Anastassia N. Rissanou Maria Amprazi Michael Kokkinidis Vagelis Harmandaris |
author_facet | Maria Arnittali Anastassia N. Rissanou Maria Amprazi Michael Kokkinidis Vagelis Harmandaris |
author_sort | Maria Arnittali |
collection | DOAJ |
description | In the current work we study, via molecular simulations and experiments, the folding and stability of proteins from the tertiary motif of 4-α-helical bundles, a recurrent motif consisting of four amphipathic α-helices packed in a parallel or antiparallel fashion. The focus is on the role of the loop region in the structure and the properties of the wild-type Rop (wtRop) and RM6 proteins, exploring the key factors which can affect them, through all-atom molecular dynamics (MD) simulations and supporting by experimental findings. A detailed investigation of structural and conformational properties of wtRop and its RM6 loopless mutation is presented, which display different physical characteristics even in their native states. Then, the thermal stability of both proteins is explored showing RM6 as more thermostable than wtRop through all studied measures. Deviations from native structures are detected mostly in tails and loop regions and most flexible residues are indicated. Decrease of hydrogen bonds with the increase of temperature is observed, as well as reduction of hydrophobic contacts in both proteins. Experimental data from circular dichroism spectroscopy (CD), are also presented, highlighting the effect of temperature on the structural integrity of wtRop and RM6. The central goal of this study is to explore on the atomic level how a protein mutation can cause major changes in its physical properties, like its structural stability. |
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issn | 1661-6596 1422-0067 |
language | English |
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spelling | doaj.art-2370678ac17540f5ab8a87969af458c72023-11-21T22:18:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211593110.3390/ijms22115931Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and ExperimentsMaria Arnittali0Anastassia N. Rissanou1Maria Amprazi2Michael Kokkinidis3Vagelis Harmandaris4Institute of Applied and Computational Mathematics (IACM), Foundation for Research and Technology Hellas (FORTH), IACM/FORTH, GR-71110 Heraklion, Crete, GreeceInstitute of Applied and Computational Mathematics (IACM), Foundation for Research and Technology Hellas (FORTH), IACM/FORTH, GR-71110 Heraklion, Crete, GreeceDepartment of Biology, University of Crete, GR-71409 Heraklion, Crete, GreeceDepartment of Biology, University of Crete, GR-71409 Heraklion, Crete, GreeceInstitute of Applied and Computational Mathematics (IACM), Foundation for Research and Technology Hellas (FORTH), IACM/FORTH, GR-71110 Heraklion, Crete, GreeceIn the current work we study, via molecular simulations and experiments, the folding and stability of proteins from the tertiary motif of 4-α-helical bundles, a recurrent motif consisting of four amphipathic α-helices packed in a parallel or antiparallel fashion. The focus is on the role of the loop region in the structure and the properties of the wild-type Rop (wtRop) and RM6 proteins, exploring the key factors which can affect them, through all-atom molecular dynamics (MD) simulations and supporting by experimental findings. A detailed investigation of structural and conformational properties of wtRop and its RM6 loopless mutation is presented, which display different physical characteristics even in their native states. Then, the thermal stability of both proteins is explored showing RM6 as more thermostable than wtRop through all studied measures. Deviations from native structures are detected mostly in tails and loop regions and most flexible residues are indicated. Decrease of hydrogen bonds with the increase of temperature is observed, as well as reduction of hydrophobic contacts in both proteins. Experimental data from circular dichroism spectroscopy (CD), are also presented, highlighting the effect of temperature on the structural integrity of wtRop and RM6. The central goal of this study is to explore on the atomic level how a protein mutation can cause major changes in its physical properties, like its structural stability.https://www.mdpi.com/1422-0067/22/11/5931biomoleculesRopRM6proteinsmolecular dynamics simulationsmutations |
spellingShingle | Maria Arnittali Anastassia N. Rissanou Maria Amprazi Michael Kokkinidis Vagelis Harmandaris Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments International Journal of Molecular Sciences biomolecules Rop RM6 proteins molecular dynamics simulations mutations |
title | Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments |
title_full | Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments |
title_fullStr | Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments |
title_full_unstemmed | Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments |
title_short | Structure and Thermal Stability of wtRop and RM6 Proteins through All-Atom Molecular Dynamics Simulations and Experiments |
title_sort | structure and thermal stability of wtrop and rm6 proteins through all atom molecular dynamics simulations and experiments |
topic | biomolecules Rop RM6 proteins molecular dynamics simulations mutations |
url | https://www.mdpi.com/1422-0067/22/11/5931 |
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