scholarly journals Dynamics of camel and human hemoglobin revealed by molecular simulations

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanat Ali ◽  
Soja Saghar Soman ◽  
Ranjit Vijayan
Keyword(s):  
Physiological Stress ◽  
Experimental Studies ◽  
Oxygen Binding ◽  
Human Hemoglobin ◽  
Heme Group ◽  
Structural Variations ◽  
Physiological Conditions ◽  
Cofactor Binding ◽  
Dynamics Simulations ◽  
T State

AbstractHemoglobin is one of the most widely studied proteins genetically, biochemically, and structurally. It is an oxygen carrying tetrameric protein that imparts the characteristic red color to blood. Each chain of hemoglobin harbors a heme group embedded in a hydrophobic pocket. Several studies have investigated structural variations present in mammalian hemoglobin and their functional implications. However, camel hemoglobin has not been thoroughly explored, especially from a structural perspective. Importantly, very little is known about how the heme group interacts with hemoglobin under varying conditions of osmolarity and temperature. Several experimental studies have indicated that the tense (T) state is more stable than the relaxed (R) state of hemoglobin under normal physiological conditions. Despite the fact that R state is less stable than the T state, no extensive structural dynamics studies have been performed to investigate global quaternary transitions of R state hemoglobin under normal physiological conditions. To evaluate this, several 500 ns all-atom molecular dynamics simulations were performed to get a deeper understanding of how camel hemoglobin behaves under stress, which it is normally exposed to, when compared to human hemoglobin. Notably, camel hemoglobin was more stable under physiological stress when compared to human hemoglobin. Additionally, when compared to camel hemoglobin, cofactor-binding regions of hemoglobin also exhibited more fluctuations in human hemoglobin under the conditions studied. Several differences were observed between the residues of camel and human hemoglobin that interacted with heme. Importantly, distal residues His58 of α hemoglobin and His63 of β hemoglobin formed more sustained interactions, especially at higher temperatures, in camel hemoglobin. These residues are important for oxygen binding to hemoglobin. Thus, this work provides insights into how camel and human hemoglobin differ in their interactions under stress.

scholarly journals Comment on ‘Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size’

2019 ◽  
Author(s):  
Vytautas Gapsys ◽  
Bert L. de Groot
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Size Dependence ◽  
Conformational Transitions ◽  
Human Hemoglobin ◽  
Order Of Magnitude ◽  
The Stability ◽  
Dynamics Simulations ◽  
T State

AbstractA recent molecular dynamics investigation into the stability of hemoglobin concluded that the unliganded protein is only stable in the T state when a solvent box is used in the simulations that is ten times larger than what is usually employed. Here, we express three main concerns about that study. In addition, we show that with an order of magnitude more statistics, the reported box size dependence is not reproducible. Overall, no significant effects on the kinetics or thermodynamics of conformational transitions were observed.

scholarly journals Comment on 'Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size'

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Vytautas Gapsys ◽  
Bert L de Groot
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Size Dependence ◽  
Conformational Transitions ◽  
Human Hemoglobin ◽  
Order Of Magnitude ◽  
The Stability ◽  
Dynamics Simulations ◽  
T State

A recent molecular dynamics investigation into the stability of hemoglobin concluded that the unliganded protein is only stable in the T state when a solvent box is used in the simulations that is ten times larger than what is usually employed (El Hage et al., 2018). Here, we express three main concerns about that study. In addition, we find that with an order of magnitude more statistics, the reported box size dependence is not reproducible. Overall, no significant effects on the kinetics or thermodynamics of conformational transitions were observed.

An intervention study on the effectiveness of an anti-stress-app on psychophysiological acute and chronic stress (Preprint)

2018 ◽  
Author(s):  
Franziska Lautenbach
Keyword(s):  
Chronic Stress ◽  
Acute Stress ◽  
Physiological Stress ◽  
Stress Test ◽  
Experimental Studies ◽  
Trier Social Stress Test ◽  
Control Group ◽  
Subjective Perception ◽  
Face To Face ◽  
Acute And Chronic Stress

BACKGROUND Dealing with stress is of central importance. Lately, smartphone applications (apps) are deployed in stress interventions as they offer maximal flexibility for users. First results of experimental studies show that anti-stress apps effect subjective perception of stress positively (Ly et al., 2014). However, current literature lacks studies on physiological stress reactions (e.g., cortisol), although they are of special interest to health issues. OBJECTIVE Therefore, the aim of this study was to investigate the effectiveness of an anti-stress app in chronic and acute stress reduction on a physiological (cortisol) and psychological level (subjective perception of stress) in comparison to a face-to-face and a control group in a pre-post design, for the first time. METHODS Sixty-two participants took part in the pretesting procedure (drop-out of 53 %). Based on age, gender, physical activity and subjectively perceived acute stress due to the Trier Social Stress Test for groups (TSST-G; von Dawans et al., 2011) as well as based on subjectively chronic stress assessed during the pretest, participants were parallelized in three groups (anti-stress-app: n = 10, face-to-face: n = 11, control group: n = 9). RESULTS After six weeks of the cognitive-based resource-oriented intervention, participants were exposed to the TSST-G for post testing. Results did not show a change of cortisol secretion or cognitive appraisal of the acute stressor. Further, no changes were detected in the chronic physiological stress reaction. CONCLUSIONS Possible causes are discussed extensively. CLINICALTRIAL no

scholarly journals The structural plasticity of nucleic acid duplexes revealed by WAXS and MD

2021 ◽  
Vol 7 (17) ◽  
pp. eabf6106
Author(s):  
Weiwei He ◽  
Yen-Lin Chen ◽  
Lois Pollack ◽  
Serdal Kirmizialtin
Keyword(s):  
Structural Diversity ◽  
Conformational Ensemble ◽  
Structural Variations ◽  
Dna And Rna ◽  
X Ray Scattering ◽  
Double Stranded Dna ◽  
Binding Partners ◽  
Rna Duplexes ◽  
Dynamics Simulations ◽  
Integrate Solution

Double-stranded DNA (dsDNA) and RNA (dsRNA) helices display an unusual structural diversity. Some structural variations are linked to sequence and may serve as signaling units for protein-binding partners. Therefore, elucidating the mechanisms and factors that modulate these variations is of fundamental importance. While the structural diversity of dsDNA has been extensively studied, similar studies have not been performed for dsRNA. Because of the increasing awareness of RNA’s diverse biological roles, such studies are timely and increasingly important. We integrate solution x-ray scattering at wide angles (WAXS) with all-atom molecular dynamics simulations to explore the conformational ensemble of duplex topologies for different sequences and salt conditions. These tightly coordinated studies identify robust correlations between features in the WAXS profiles and duplex geometry and enable atomic-level insights into the structural diversity of DNA and RNA duplexes. Notably, dsRNA displays a marked sensitivity to the valence and identity of its associated cations.

scholarly journals Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renu Wadhwa ◽  
Neetu Singh Yadav ◽  
Shashank P. Katiyar ◽  
Tomoko Yaguchi ◽  
Chohee Lee ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Molecular Dynamics Simulations ◽  
Experimental Studies ◽  
Bilayer Membrane ◽  
Withaferin A ◽  
Head Group ◽  
Polar Head Group ◽  
Natural Drugs ◽  
Dynamics Simulations

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs—withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability. The free energy profiles for the interaction of withanolides with the model bilayer membrane revealed that whereas the polar head group of the membrane caused high resistance for the passage of withanone, the interior of the membrane behaves similarly for both withanolides. The solvation analysis further revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force for its high permeability; it interacted with the phosphate group of the membrane that led to its smooth passage across the bilayer. The computational predictions were tested by raising and recruiting unique antibodies that react to withaferin-A and withanone. The time-lapsed analyses of control and treated cells demonstrated higher permeation of withaferin-A as compared to withanone. The concurrence between the computation and experimental results thus re-emphasised the use of computational methods for predicting permeability and hence bioavailability of natural drug compounds in the drug development process.

Asymmetric Distribution of Cooperativity in the Binding Cascade of Normal Human Hemoglobin. 1. Cooperative and Noncooperative Oxygen Binding in Zn-Substituted Hemoglobin†

Biochemistry ◽  
2005 ◽  
Vol 44 (36) ◽  
pp. 11925-11938 ◽  
Author(s):  
Jo M. Holt ◽  
Alexandra L. Klinger ◽  
Connie S. Yarian ◽  
Varsha Keelara ◽  
Gary K. Ackers
Keyword(s):  
Asymmetric Distribution ◽  
Oxygen Binding ◽  
Human Hemoglobin ◽  
Normal Human

Possible Mechanisms for Thermal Conductivity Enhancement in Nanofluids

2006 ◽  
Author(s):  
Amit Gupta ◽  
Xuan Wu ◽  
Ranganathan Kumar
Keyword(s):  
Heat Transfer ◽  
Thermal Conductivity ◽  
Brownian Motion ◽  
Brownian Dynamics ◽  
Lattice Vibration ◽  
Experimental Studies ◽  
High Heat ◽  
Conductivity Enhancement ◽  
High Heat Transfer ◽  
Dynamics Simulations

This study discusses the merits of various physical mechanisms that are responsible for enhancing the heat transfer in nanofluids. Experimental studies have cemented the claim that ‘seeding’ liquids with nanoparticles can increase the thermal conductivity of the nanofluid by up to 40% for metallic and oxide nanoparticles dispersed in a base liquid. Experiments have also shown that the rise in conductivity of the nanofluid is highly dependent on the size and concentration of the nanoparticles. On the theoretical side, traditional models like Maxwell or Hamilton-Crosser models cannot explain this unusually high heat transfer. Several mechanisms have been postulated in the literature such as Brownian motion, thermal diffusion in nanoparticles and thermal interaction of nanoparticles with the surrounding fluid, the formation of an ordered liquid layer on the surface of the nanoparticle and microconvection. This study concentrates on 3 possible mechanisms: Brownian dynamics, microconvection and lattice vibration of nanoparticles in the fluid. By considering two nanofluids, copper particles dispersed in ethylene glycol, and silica in water, it is determined that translational Brownian motion of the nanoparticles, presence of an interparticle potential and the microconvection heat transfer are mechanisms that play only a smaller role in the enhancement of thermal conductivity. On the other hand, the lattice vibrations, determined by molecular dynamics simulations show a great deal of promise in increasing the thermal conductivity by as much as 23%. In a simplistic sense, the lattice vibration can be regarded as a means to simulate the phononic transport from solid to liquid at the interface.

scholarly journals The role of amino acid α38 in the control of oxygen binding to human adult and embryonic haemoglobin Portland

1999 ◽  
Vol 343 (3) ◽  
pp. 681-685 ◽  
Author(s):  
Tao ZHENG ◽  
Thomas BRITTAIN ◽  
Nicholas J. WATMOUGH ◽  
Roy E. WEBER
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Significant Contribution ◽  
Molecular Model ◽  
Site Directed Mutagenesis ◽  
Oxygen Binding ◽  
Naturally Occurring ◽  
Two State Model ◽  
T State

The role of the amino acid at position α38 in haemoglobin has been probed using site-directed mutagenesis. When the Thr residue at position α38 (which is totally conserved in all mammals) is changed to a Gln, the equilibrium properties of the protein are significantly altered. Equilibrium and kinetic data show that the R-state properties of the protein are essentially unaffected by the mutation whilst the allosteric equilibrium and T-state properties are changed. Mutation of the naturally occurring Gln38 of the human embryonic haemoglobin ζ-chain (the only known non-Thr containing globin) to a Thr residue shows the converse change in properties produced by the adult mutation, although in this case the situation is complicated by significant chain heterogeneity in the T state. An extension of the two-state model of co-operativity is presented to describe quantitatively the equilibrium ligand binding in the presence of T-state chain heterogeneity. A molecular model is described in which the putative interaction of αGln38 and βTyr145 is identified which make a significant contribution to the previously reported unusual ligand-binding properties of the ζ-chain containing human embryonic haemoglobins.

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