Electronic fluctuation difference between trimethylamine N-oxide and tert-butyl alcohol in water

Kuroki, Nahoko; Uchino, Yukina; Funakura, Tamon; Mori, Hirotoshi

doi:10.1038/s41598-022-24049-0

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…43,65 Ab initio MD simulations indicated slow dynamics for the water molecules in TMAO solutions, where the water molecules and TMAO interact strongly. 66 These findings are consistent with our simulation results. For TMAO solutions, the previous classical all-atomic MD simulations showed that the number of neighboring water molecules decreases, whereas the water−water hydrogen bond network is relatively enhanced, leading to the slower relaxation of the hydrogen bonds between water molecules.…”

Section: ■ Discussionsupporting

confidence: 92%

“…The rotational dynamics of the GB, urea, and TMAO solutions and the pure water system were in agreement with the results of classical all-atomic MD simulations reported previously. , Ab initio MD simulations indicated slow dynamics for the water molecules in TMAO solutions, where the water molecules and TMAO interact strongly . These findings are consistent with our simulation results.…”

Section: Discussionmentioning

confidence: 99%

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Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations

Higuchi,

Saleh,

Anada

et al. 2024

J. Phys. Chem. B

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The behavior of water molecules around organic molecules has attracted considerable attention as a crucial factor influencing the properties and functions of soft matter and biomolecules. Recently, it has been suggested that the change in protein stability upon the addition of small organic molecules (osmolytes) is dominated by the change in the water dynamics caused by the osmolyte, where the dynamics of not only the directly interacting water molecules but also the long-range hydration layer affect the protein stability. However, the relation between the long-range structure of hydration water in various solutions and the water dynamics remains unclear at the molecular level. We performed density-functional tight-binding molecular dynamics simulations to elucidate the varying rotational dynamics of water molecules in 15 osmolyte solutions. A positive correlation was observed between the rotational relaxation time and our proposed normalized parameter obtained by dividing the number of hydrogen bonds between water molecules by the number of nearest-neighbor water molecules. For the 15 osmolyte solutions, an increase or a decrease in the value of the normalized parameter for the second hydration shell tended to result in water molecules with slow and fast rotational dynamics, respectively, thus illustrating the importance of the second hydration shell for the rotational dynamics of water molecules. Our simulation results are anticipated to advance the current understanding of water dynamics around organic molecules and the long-range structure of water molecules.

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Section: ■ Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations

Higuchi,

Saleh,

Anada

et al. 2024

J. Phys. Chem. B

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“…Importantly, TMAO does not physically interact with either proteins 51–53 or lipids 20,21,54 but rather interacts with the surrounding water molecules 53 . Furthermore, the high TMAO dipole moment modifies water distribution around it 55 . Therefore, given the ubiquitous nature of TMAO-water interactions, we anticipate TMAO to impact a vast majority of proteins and lipids in the cell.…”

Section: Discussionmentioning

confidence: 99%

TMAO miscompartmentalization is a reversible driver of autism pathophysiology

Launay,

Vodovar

2024

Preprint

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Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder. Contrary to what has been reported for genetics and gut dysbiosis, ASD appears to be very homogeneous when considering tryptophan metabolism. Indeed, multiple biochemical anomalies have been observed in most individuals with ASD. Following up on these findings, we found that ASD is strongly associated with the miscompartmentalization of the chemical chaperone trimethylamineN-oxide (TMAO). Intracellular TMAO was markedly reduced in individuals with ASD as a result of altered fluid/electrolyte homeostasis and was responsible for numerous biochemical anomalies described in ASD. Administration of urea in a rat model of ASD that recapitulates the biochemical anomalies observed in humans not only restored biochemical parameters but also broadly improved all behaviours. Our results demonstrate the major role of TMAO in the pathophysiology of ASD and cellular physiology, although TMAO miscompartmentalization is not causal for ASD. We anticipate that urea, which is already clinically approved, offers a breakthrough therapeutic opportunity for ASD.

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“…30 Our group also reported the possibility of explaining life phenomena using EFP and FMO and their compatibility with machine learning techniques. [31][32][33][34][35] A systematic definition of the QM regions using fragmentation methods would solve the computational cost problem.…”

Section: Introductionmentioning

confidence: 99%

Biological Active Region Defined by Fragment-based Molecular Theory

Ozawa,

Mori,

Kuroki

2024

Preprint

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Computational chemistry studies using the QM/MM approach have been conducted to explain and predict protein functions. However, the active regions responsible for those functions often need to be clarified. In this paper, we propose a simple method to define the active region of a ligand from its physicochemical components using the fragment molecular orbital theory. This method systematically determines the QM region in QM/MM calculations by considering quantum interactions among amino acid residues, i.e., charge transfer relays. Within proteins, the relays occur through the interaction network formed among residues, and this phenomenon may interfere with the determination of the QM region. We determined the quantum chemical active region by analyzing the difference in the charge transfer relay upon ligand binding to the protein. Defining the active region as the domain where these relays converge, we successfully reproduce the experimental activity qualitatively; our definition of the active region is reliable. The proposed method defines the QM region easily and unambiguously and is expected to aid in bio-relevant chemistry and drug discovery.

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Electronic fluctuation difference between trimethylamine N-oxide and tert-butyl alcohol in water

Cited by 4 publications

References 37 publications

Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations

Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations

TMAO miscompartmentalization is a reversible driver of autism pathophysiology

Biological Active Region Defined by Fragment-based Molecular Theory

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