Dynamics of urea-water mixtures studied by molecular dynamics simulation

Lovrinčević, Bernarda; Požar, Martina; Balić, Marijana

doi:10.1016/j.molliq.2019.112268

Cited by 17 publications

(7 citation statements)

References 54 publications

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“…We turned to hydrogen bond (HB) analysis to quantify the observations from the video. The HB analysis used in this paper is a staple in the research of liquids and liquid mixtures and workers in the field have used this methodology for quantifying the hydrogen bonding process in water, − alcohols, and related mixtures. − This same analysis is relevant for studying the interaction of proteins with water, for example, in protein hydration. , In this work, we primarily focus on the interaction between metformin and the protein via Hbonding.…”

Section: Results and Discussionmentioning

confidence: 99%

Why Should Metformin Not Be Given in Advanced Kidney Disease? Potential Leads from Computer Simulations

Maleš

Požar

2021

ACS Omega

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Metformin is considered as the go-to drug in the treatment of diabetes. However, it is either prescribed in lower doses or not prescribed at all to patients with kidney problems. To find a potential explanation for this practice, we employed atomistic-level computer simulations to simulate the transport of metformin through multidrug and toxin extrusion 1 (MATE1), a protein known to play a key role in the expulsion of metformin into urine. Herein, we examine the hydrogen bonding between MATE1 and one or more metformin molecules. The simulation results indicate that metformin continuously forms and breaks off hydrogen bonds with MATE1 residues. However, the mean hydrogen bond lifetimes increase for an order of magnitude when three metformin molecules are inserted instead of one. This new insight into the metformin transport process may provide the molecular foundation behind the clinical practice of not prescribing metformin to kidney disease patients.

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Section: Results and Discussionmentioning

confidence: 99%

Why Should Metformin Not Be Given in Advanced Kidney Disease? Potential Leads from Computer Simulations

Maleš

Požar

2021

ACS Omega

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“…Moreover, the orientational relaxation time and the average lifetime of hydrogen bonds also remain the same as in neat water. Contrastingly, the hydrogen-bond correlation time function is observed to decay more slowly in urea solution than in pure water, indicating that the water network becomes rigid in urea solution . The observation of an increase in water–water hydrogen-bond energy with the increase in urea concentration also suggests urea as a structure maker …”

Section: Introductionmentioning

confidence: 89%

“…Contrastingly, the hydrogen-bond correlation time function is observed to decay more slowly in urea solution than in pure water, indicating that the water network becomes rigid in urea solution. 45 The observation of an increase in water−water hydrogen-bond energy with the increase in urea concentration also suggests urea as a structure maker. 42 Trehalose has been observed to destruct the tetrahedral hydrogen-bond network of water because of the decrease in water−water hydrogen bonds.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Numerous computational studies have also investigated the structure and dynamics of water in the presence of osmolytes in binary solutions. ,,,− The water–water radial distribution function (rdf) and the spatial density of water indicate a slight collapse of the second solvation shell of water in 5 M urea solution . The number of hydrogen bonds per water molecule is, however, almost the same as in neat water (NW) − when urea is also considered as the hydrogen-bond partner for the water molecule, revealing that urea very well substitutes for water in the hydrogen-bond network.…”

Section: Introductionmentioning

confidence: 99%

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Unraveling the Influence of Osmolytes on Water Hydrogen-Bond Network: From Local Structure to Graph Theory Analysis

Sundar

Sandilya

Priya

2021

J. Chem. Inf. Model.

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Water structure in aqueous osmolyte solutions, deduced from the slight alteration in the water−water radial distribution function, the decrease in water−water hydrogen bonding, and tetrahedral ordering based only on the orientation of nearest water molecules derived from the molecular dynamics simulations, appears to have been perturbed. A careful analysis, however, reveals that the hydrogen bonding and the tetrahedral ordering around a water molecule in binary solutions remain intact as in neat water when the contribution of osmolyte−water interactions is appropriately incorporated. Furthermore, the distribution of the water binding energies and the water excess chemical potential of solvation in solutions are also pretty much the same as in neat water. Osmolytes are, therefore, well integrated into the hydrogen-bond network of water. Indeed, osmolytes tend to preferentially hydrogen bond with water molecules and their interaction energies are strongly correlated to their hydrogen-bonding capability. The graph network analysis, further, illustrates that osmolytes act as hubs in the percolated hydrogen-bond network of solutions. The degree of hydrogen bonding of osmolytes predominantly determines all of the network properties. Osmolytes like ethanol that form fewer hydrogen bonds than a water molecule disrupt the water hydrogen-bond network, while other osmolytes that form more hydrogen bonds effectively increase the connectivity among water molecules. Our observation of minimal variation in the local structure and the vitality of osmolyte−water hydrogen bonds on the solution network properties clearly imply that the direct interaction between protein and osmolytes is solely responsible for the protein stability. Further, the relevance of hydrogen bonds on solution properties suggests that the hydrogen-bonding interaction among protein, water, and osmolyte could be the key determinant of the protein conformation in solutions.

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“…It destabilizes the folded state of a protein and stabilizes the unfolded state. For this reason, the molecular action of urea in aqueous medium has received much attention both experimentally and theoretically. − Urea is an amphiphile which possesses both hydrophilic and hydrophobic moieties. It has been shown by some of the experimental and simulation studies ,,,− ,, that in binary aqueous solutions, urea molecules weakly perturb the hydrogen-bonded network of water without significantly affecting its vibrational and structural properties.…”

Section: Introductionmentioning

confidence: 99%

Counteracting Effects of TrimethylamineN-Oxide against Urea in Aqueous Solutions: Insights from Theoretical Two-Dimensional Infrared Spectroscopy

Malik,

Chandra

2023

J. Phys. Chem. B

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The study of small osmolytes in their aqueous solutions has gained significant attention because of their relevance to structure and thermodynamics of proteins in aqueous media. Special attention has been given to the binary and ternary aqueous solutions of urea and trimethylamine N-oxide (TMAO). Urea is a well-known protein denaturant, while TMAO protects proteins in their native states. Interestingly, TMAO counteracts urea's ability to denature proteins when present in solutions with approximately half of the concentration of urea. Vibrational spectroscopy can improve our understanding of the molecular origin of this counteracting effect because of its sensitivity to local structure and dynamics. We present results of theoretical linear vibrational and two-dimensional infrared (2DIR) spectroscopy of water in the binary and ternary aqueous solutions of TMAO and urea. The 2DIR spectra are calculated using the electronic structure/molecular dynamics approach. The non-Condon effects in spectral transitions are incorporated in the theoretical calculations of 2DIR spectra. It is found that TMAO disrupts the local structure of water, while urea leaves it essentially unaffected. The 2DIR results show that both TMAO and urea slow down the dynamics of spectral diffusion of water. The extent of slowing down is found to be particularly significant for both hydration and bulk water in the presence of TMAO which can be attributed to strong hydrogen bonds between the water and TMAO molecules. The water molecules present in the hydration layer of the solutes in the ternary solutions are found to relax at even slower rates compared to that in their binary solutions in water. The hydrogen bonds between TMAO and urea are found to be not stable. Thus, the counteracting effect of TMAO against urea is seen to take place mainly through water-mediated interactions. Such TMAO-induced effects giving rise to more structured and slower hydrogen-bonded network are successfully captured through 2DIR spectroscopic calculations.

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Dynamics of urea-water mixtures studied by molecular dynamics simulation

Cited by 17 publications

References 54 publications

Why Should Metformin Not Be Given in Advanced Kidney Disease? Potential Leads from Computer Simulations

Why Should Metformin Not Be Given in Advanced Kidney Disease? Potential Leads from Computer Simulations

Unraveling the Influence of Osmolytes on Water Hydrogen-Bond Network: From Local Structure to Graph Theory Analysis

Counteracting Effects of TrimethylamineN-Oxide against Urea in Aqueous Solutions: Insights from Theoretical Two-Dimensional Infrared Spectroscopy

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