Thermal stability and unfolding pathways of hyperthermophilic and mesophilic periplasmic binding proteins studied by molecular dynamics simulation

Chen, Lin; Li, Xue; Wang, Ruige; Fang, Fengqin; Yang, Wanli; Kan, Wei

doi:10.1080/07391102.2015.1084480

Cited by 7 publications

(5 citation statements)

References 42 publications

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“…In the present study, the protein was solvated using the SPC model . This model has been successfully applied into a variety of thermal unfolding studies. − A cubic box was constructed to perform MD simulations. Water molecules that overlapped with the protein heavy atoms were removed.…”

Section: System and Methodsmentioning

confidence: 99%

Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12

Jiang

Chen

et al. 2017

J. Chem. Inf. Model.

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The temperature dependence of enzyme catalysis is highly debated. Specifically, how high temperatures induce enzyme inactivation has broad implications for both fundamental and applied science. Here, we explored the mechanism of the reversible thermal inactivation in glycoside hydrolase family 12 (GH12) using comparative molecular dynamics simulations. First, we investigated the distribution of structural flexibility over the enzyme and found that the active site was the general thermal-sensitive region in GH12 cellulases. The dynamic perturbation of the active site before enzyme denaturation was explored through principal-component analysis, which indicated that variations in the collective motion and conformational ensemble of the active site may precisely correspond to enzyme transition from its active form to the inactive form. Furthermore, the degree of dynamic perturbation of the active site was found to be negatively correlated with the melting temperatures of GH12 enzymes, further proving the importance of the dynamic stability of the active site. Additionally, analysis of the residue-interaction network revealed that the active site in thermophilic enzyme was capable of forming additional contacts with other amino acids than those observed in the mesophilic enzyme. These interactions are likely the key mechanisms underlying the differences in rigidity of the active site. These findings provide further biophysical insights into the reversible thermal inactivation of enzymes and potential applications in future protein engineering.

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Section: System and Methodsmentioning

confidence: 99%

Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12

Jiang

Chen

et al. 2017

J. Chem. Inf. Model.

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“…This behavior can be attributed to hydrogen bonding, salt bridges, van der Waals’ interactions, hydrophobic internal packing, improved electrostatic interactions, and others [ 21 , 22 ]. Currently, molecular dynamics simulation techniques allow us to understand the behavior of many proteins submitted to high temperatures, and to enable us to predict their behavior [ 23 , 24 , 25 , 26 ]. For example, the soy allergen has been analyzed by molecular dynamics simulations methods to understand the structural conformation for the development of antiallergenic drugs [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Heat-Stable Hazelnut Profilin: Molecular Dynamics Simulations and Immunoinformatics Analysis

et al. 2020

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Heat treatment can modify the allergenic potential, reducing allergenicity in specific proteins. Profilins are one of the important hazelnut allergens; these proteins are considered panallergens due to their high capacity for cross-reactivity with other allergens. In the present work, we evaluated the thermostability of hazelnut profilin, combining molecular dynamics simulation and immunoinformatic techniques. This approach helped us to have reliable results in immunogenicity studies. We modeled Cor a 2 profilin and applied annealing simulation, equilibrium, and production simulation at constant temperatures ranging from 300 to 500 K using Gromacs software. Despite the hazelnut profilins being able to withstand temperatures of up to 400 K, this does not seem to reduce its allergenicity. We have found that profilin subjected to temperatures of 450 and 500 K could generate cross-reactivity with other food allergens. In conclusion, we note a remarkable thermostability of Cor a 2 at 400 K which avoids its structural unfolding.

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“…In particular, MD is traditionally used for studying the thermal stability of nanostructures, nanomaterials, and biomolecules. [1][2][3] On the other hand, the so-called "time-scale problem" 4,5 is a well-known drawback of traditional MD approach. This problem arises from a huge mismatch between typical MD time step ~0.1 fs, required for the adequate treating of atomic oscillations, and characteristic times of the studied processes, that can be rather macroscopic.…”

Section: Introductionmentioning

confidence: 99%

“…MD provides observation of the considered system evolution in a “real-time mode”, and therefore, it is the direct way to simulate any kinetic process occurring at the atomic level. In particular, MD is traditionally used for studying the thermal stability of nanostructures, nanomaterials, and biomolecules. − …”

Section: Introductionmentioning

confidence: 99%

Molecular Hyperdynamics Coupled with the Nonorthogonal Tight-Binding Approach: Implementation and Validation

Katin¹,

Гришаков²,

Подливаев³

et al. 2020

J. Chem. Theory Comput.

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We present the molecular hyperdynamics algorithm and its implementation to the nonorthogonal tight-binding model NTBM and the corresponding software. Due to its multiscale structure, the proposed approach provides the long time scale simulations (more than 1 s), unavailable for conventional molecular dynamics. No preliminary information about the system potential landscape is needed for the use of this technique. The optimal interatomic potential modification is automatically derived from the previous simulation steps. The average time between adjusted potential energy fluctuations provides an accurate evaluation of physical time during the hyperdynamics simulation. The main application of the presented hyperdynamics method is the study of thermal-induced defects arising in the middle-sized or relatively large atomic systems at low temperatures. To validate the presented method, we apply it to the C60 cage and its derivative C60NH2.Hyperdynamics leads to the same results as a conventional molecular dynamics, but the former possesses much higher performance and accuracy due to the wider temperature region. The coefficient of acceleration achieves 10 7 and more. Straight lines are the linear approximations of these dependencies by the Arrhenius lawwhere  is the time that is needed for the corresponding reaction, Ea is the activation energy, kB is the Boltzmann's constant, T is the temperature. Activation energies can be derived from the slopes of approximating lines. Both MD and hyperdynamics methods predict the formation of the same Stone-Wales defect imaged in Fig. 2a. We obtain the reasonably good agreement of reaction times predicted using these methods, see Fig. 2a. Corresponding activation energies are equal to 6.22 ± 0.99 and 6.44 ± 0.22 eV for MD and hyperdynamics, respectively, see Fig. 3a. They match with the previously reported corresponding energy barrier (6.48 eV 27 ). One can see the high accuracy of hyperdynamics associated with the wide available temperature range. Note, that hyperdynamics provides reaction times of 1 s and more, whereas the comparable number of MD steps can provide only tens of nanoseconds. So, the acceleration factor due to the use of hyperdynamics reaches 10 7 and more.During the studying of heated C60NH2 cage, we observe two possible events: the C-N bond fission ( Fig. 2b) and the formation of bridge configuration with tetra-coordinated nitrogen (Fig. 2c).The latter appears only at very high temperatures (T ≥ 1800 K). Thus, we ignored this scenario in the activation energy evaluation. Such example confirms the importance of accounting for the lowtemperature region to get the actual reaction mechanism. For the fission of the C-N bond, we obtain the activation energies of 3.66 ± 0.55 and 3.28 ± 0.21 eV for MD and hyperdynamics methods, respectively. These values are close to the previously reported binding energies between NH2 functional group and small carbon nanotubes (2.5 ÷ 3.5 eV depending on the tube's chirality indices 28 ). Figure 3b demonstrates reasonably well agreement ...

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Thermal stability and unfolding pathways of hyperthermophilic and mesophilic periplasmic binding proteins studied by molecular dynamics simulation

Cited by 7 publications

References 42 publications

Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12

Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12

Heat-Stable Hazelnut Profilin: Molecular Dynamics Simulations and Immunoinformatics Analysis

Molecular Hyperdynamics Coupled with the Nonorthogonal Tight-Binding Approach: Implementation and Validation

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