scholarly journals Effects of Pressure and Temperature on the Atomic Fluctuations of Dihydrofolate Reductase from a Psychropiezophile and a Mesophile

2019 ◽  
Vol 20 (6) ◽  
pp. 1452 ◽  
Author(s):  
Qi Huang ◽  
Jocelyn Rodgers ◽  
Russell Hemley ◽  
Toshiko Ichiye
Keyword(s):  
Hydrogen Bonds ◽  
Dihydrofolate Reductase ◽  
Thermal Energy ◽  
Food Preservation ◽  
Enzyme Function ◽  
Extreme Conditions ◽  
Loop Regions ◽  
Temperature And Pressure ◽  
Moritella Profunda ◽  
Dynamics Simulations

Determining the effects of extreme conditions on proteins from “extremophilic” and mesophilic microbes is important for understanding how life adapts to living at extremes as well as how extreme conditions can be used for sterilization and food preservation. Previous molecular dynamics simulations of dihydrofolate reductase (DHFR) from a psychropiezophile (cold- and pressure-loving), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec), at various pressures and temperatures indicate that atomic fluctuations, which are important for enzyme function, increase with both temperature and pressure. Here, the factors that cause increases in atomic fluctuations in the simulations are examined. The fluctuations increase with temperature not only because of greater thermal energy and thermal expansion of the protein but also because hydrogen bonds between protein atoms are weakened. However, the increase in fluctuations with pressure cannot be due to thermal energy, which remains constant, nor the compressive effects of pressure, but instead, the hydrogen bonds are also weakened. In addition, increased temperature causes larger increases in fluctuations of the loop regions of MpDHFR than EcDHFR, and increased pressure causes both increases and decreases in fluctuations of the loops, which differ between the two.

scholarly journals Adaptations for Pressure and Temperature in Dihydrofolate Reductases

2021 ◽  
Vol 9 (8) ◽  
pp. 1706
Author(s):  
Ryan W. Penhallurick ◽  
Maya D. Durnal ◽  
Alliyah Harold ◽  
Toshiko Ichiye
Keyword(s):  
Hydrogen Bond ◽  
Dihydrofolate Reductase ◽  
Evolutionary History ◽  
Experimental Studies ◽  
Extreme Conditions ◽  
Extreme Temperatures ◽  
Dihydrofolate Reductases ◽  
History Of ◽  
Moritella Profunda ◽  
Dynamics Simulations

Enzymes from extremophilic microbes that live in extreme conditions are generally adapted so that they function under those conditions, although adaptations for extreme temperatures and pressures can be difficult to unravel. Previous studies have shown mutation of Asp27 in Escherichia coli dihydrofolate reductase (DHFR) to Glu27 in Moritella profunda (Mp). DHFR enhances activity at higher pressures, although this may be an adaptation for cold. Interestingly, MpDHFR unfolds at ~70 MPa, while Moritella yayanosii (My) was isolated at depths corresponding to ~110 MPa, indicating that MyDHFR might be adapted for higher pressures. Here, these adaptations are examined using molecular dynamics simulations of DHFR from different microbes in the context of not only experimental studies of activity and stability of the protein but also the evolutionary history of the microbe. Results suggest Tyr103 of MyDHFR may be an adaptation for high pressure since Cys103 in helix F of MpDHFR forms an intra-helix hydrogen bond with Ile99 while Tyr103 in helix F of MyDHFR forms a hydrogen bond with Leu78 in helix E. This suggests the hydrogen bond between helices F and E in MyDHFR might prevent distortion at higher pressures.

scholarly journals Pressure Adaptations in Deep-Sea Moritella Dihydrofolate Reductases: Compressibility versus Stability

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1211
Author(s):  
Ryan W. Penhallurick ◽  
Toshiko Ichiye
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Dihydrofolate Reductase ◽  
Deep Sea ◽  
Water Entry ◽  
Internal Cavity ◽  
Cavity Volume ◽  
Dihydrofolate Reductases ◽  
Moritella Profunda ◽  
Dynamics Simulations

Proteins from “pressure-loving” piezophiles appear to adapt by greater compressibility via larger total cavity volume. However, larger cavities in proteins have been associated with lower unfolding pressures. Here, dihydrofolate reductase (DHFR) from a moderate piezophile Moritella profunda (Mp) isolated at ~2.9 km in depth and from a hyperpiezophile Moritella yayanosii (My) isolated at ~11 km in depth were compared using molecular dynamics simulations. Although previous simulations indicate that MpDHFR is more compressible than a mesophile DHFR, here the average properties and a quasiharmonic analysis indicate that MpDHFR and MyDHFR have similar compressibilities. A cavity analysis also indicates that the three unique mutations in MyDHFR are near cavities, although the cavities are generally similar in size in both. However, while a cleft overlaps an internal cavity, thus forming a pathway from the surface to the interior in MpDHFR, the unique residue Tyr103 found in MyDHFR forms a hydrogen bond with Leu78, and the sidechain separates the cleft from the cavity. Thus, while Moritella DHFR may generally be well suited to high-pressure environments because of their greater compressibility, adaptation for greater depths may be to prevent water entry into the interior cavities.

WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

2013 ◽  
Vol 12 (08) ◽  
pp. 1341002 ◽  
Author(s):  
XIN ZHANG ◽  
MING LEI
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Glutamic Acid ◽  
Active Site ◽  
Nucleophilic Attack ◽  
Zinc Ions ◽  
Initial Model ◽  
Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

scholarly journals Car–Parrinello and path integral molecular dynamics study of the intramolecular hydrogen bonds in the crystals of benzoylacetone and dideuterobenzoylacetone

2014 ◽  
Vol 16 (42) ◽  
pp. 23026-23037 ◽  
Author(s):  
Piotr Durlak ◽  
Zdzisław Latajka
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Ab Initio ◽  
Path Integral ◽  
Molecular Crystal ◽  
Short Hydrogen Bond ◽  
Deuterated Analogue ◽  
Dynamics Simulations ◽  
Intramolecular Hydrogen

The dynamics of the intramolecular short hydrogen bond in the molecular crystal of benzoylacetone and its deuterated analogue are investigated using ab initio molecular dynamics simulations.

scholarly journals The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

2013 ◽  
Vol 9 ◽  
pp. 118-134 ◽  
Author(s):  
Jutta Erika Helga Köhler ◽  
Nicole Grczelschak-Mick
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Hydrogen Bonds ◽  
Md Simulations ◽  
Benzene Molecule ◽  
Glucose Unit ◽  
Hand Orientation ◽  
Different Temperatures ◽  
Dynamics Simulations ◽  
The Right

Four highly ordered hydrogen-bonded models of β-cyclodextrin (β-CD) and its inclusion complex with benzene were investigated by three different theoretical methods: classical quantum mechanics (QM) on AM1 and on the BP/TZVP-DISP3 level of approximation, and thirdly by classical molecular dynamics simulations (MD) at different temperatures (120 K and 273 to 300 K). The hydrogen bonds at the larger O2/O3 rim of empty β-CDs prefer the right-hand orientation, e.g., O3-H…O2-H in the same glucose unit and bifurcated towards …O4 and O3 of the next glucose unit on the right side. On AM1 level the complex energy was −2.75 kcal mol−1 when the benzene molecule was located parallel inside the β-CD cavity and −2.46 kcal mol−1 when it was positioned vertically. The AM1 HOMO/LUMO gap of the empty β-CD with about 12 eV is lowered to about 10 eV in the complex, in agreement with data from the literature. AM1 IR spectra displayed a splitting of the O–H frequencies of cyclodextrin upon complex formation. At the BP/TZVP-DISP3 level the parallel and vertical positions from the starting structures converged to a structure where benzene assumes a more oblique position (−20.16 kcal mol−1 and −20.22 kcal mol−1, resp.) as was reported in the literature. The character of the COSMO-RS σ-surface of β-CD was much more hydrophobic on its O6 rim than on its O2/O3 side when all hydrogen bonds were arranged in a concerted mode. This static QM picture of the β-CD/benzene complex at 0 K was extended by MD simulations. At 120 K benzene was mobile but always stayed inside the cavity of β-CD. The trajectories at 273, 280, 290 and 300 K certainly no longer displayed the highly ordered hydrogen bonds of β-CD and benzene occupied many different positions inside the cavity, before it left the β-CD finally at its O2/O3 side.

scholarly journals A NOVEL DESIGN OF PERISTALTIC CARBON NANO PUMP AND AN ANALYSIS OF HELIUM FLOW

2021 ◽  
Vol 55 (6) ◽  
Author(s):  
M. Gokhan Günay ◽  
Ubade Kemerli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Pump Design ◽  
Helium Atoms ◽  
Multi Walled Carbon Nanotubes ◽  
Temperature And Pressure ◽  
Dynamics Simulations ◽  
Walled Carbon Nanotubes ◽  
Novel Design ◽  
Main Carbon

A novel nano-scale pump that can transport atoms or small molecules with a peristaltic motion is designed. It is proven by molecular-dynamics simulations that the introduced nano-pump design works properly. The designed nano-pump consists of one main carbon nanotube named the flow tube and two rotors where multi-walled carbon nanotubes are attached. The pumping of helium atoms by the designed peristaltic carbon nano-pump is investigated by molecular-dynamics simulations. For varying rotor speeds and blade counts, time-averaged velocity, temperature, and pressure results of pumped helium atoms are calculated, and relationships between them are modeled as polynomial surfaces. The results showed that rotor frequency increases the velocity of helium linearly and the temperature and pressure of helium non-linearly. Furthermore, the blade count of the proposed mechanism does not substantially affect the velocity as per the previous studies in the literature.

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