Shedding light on the hydrophobicity puzzle

Graziano, Giuseppe

doi:10.1515/pac-2015-1003

Cited by 27 publications

(10 citation statements)

References 60 publications

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“…This event is accompanied by an increase in the total volume available for the translational displacement of water molecules located in the system, which is in turn associated with a large gain of configurational entropy of water. [71][72][73] This hypothesis has been validated by evaluating the total (SM), hydrophilic (SM H ), and lipophilic (SM L ) surface matching between the molecules and the DP T using the PLATINUM web server 70 (Table 1, last three columns). By definition, SM is a quantity that can be correlated to the reduction of the excluded volume upon binding between molecular partners.…”

Section: Discussionmentioning

confidence: 98%

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

et al. 2019

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The drug/proton antiporter AcrB, part of the major efflux pump AcrABZ-TolC in Escherichia coli, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multidrug resistance phenotype. However, the molecular features differentiating between good and poor substrates of the pump have yet to be identified. In this work, we combined molecular docking with molecular dynamics simulations to study the interactions between AcrB and two representative cephalosporins, cefepime and ceftazidime (a good and poor substrate of AcrB, respectively). Our analysis revealed different binding preferences of the two compounds toward the subsites of the large deep binding pocket of AcrB. Cefepime, although less hydrophobic than ceftazidime, showed a higher affinity than ceftazidime for the so-called hydrophobic trap, a region known for binding inhibitors and substrates. This supports the hypothesis that surface complementarity between the molecule and AcrB, more than the intrinsic hydrophobicity of the antibiotic, is a feature required for the interaction within this region. Oppositely, the preference of ceftazidime for binding outside the hydrophobic trap might not be optimal for triggering allosteric conformational changes needed to the transporter to accomplish its function. Altogether, our findings could provide valuable information for the design of new antibiotics less susceptible to the efflux mechanism.

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Section: Discussionmentioning

confidence: 98%

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

et al. 2019

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“…Instead, we approximated r cavity,CH 4 as r cavity,CH 4 = 1 / 2 r cavity,Kr + 1 / 2 r cavity,Xe , because predicted gas–water radial distribution functions indicate that the effective radius of CH 4 in our simulations is intermediate between those of Kr and Xe. The resulting values of r cavity (calculated with r O = 1.4 Å) for He, H 2 , Ne, Ar, Kr, CH 4 , and Xe are 2.790, 2.970, 2.793, 3.082, 3.212, 3.308, and 3.405 Å, respectively. For CO 2 , we calculated the probability that two randomly placed spheres of radius r cavity = 1 / 2 σ Oc–Oc + r O = 2.917 Å (where O c is a CO 2 oxygen atom) separated by the same distance as the two oxygen atoms in CO 2 (2.3 Å) would contain no atom.…”

Section: Methodsmentioning

confidence: 99%

Hydrophobic Solvation of Gases (CO₂, CH₄, H₂, Noble Gases) in Clay Interlayer Nanopores

et al. 2017

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In the past few years, experimental studies have shown that CO 2 is roughly 5 times more soluble in watersaturated clay interlayer water than in bulk liquid water. The fundamental basis of this selectivity remains unknown, as does its relevance to other gases. Here, we use molecular dynamics (MD) simulations and gravimetric adsorption experiments to determine the solubilities of CO 2 , CH 4 , H 2 , and noble gases in clay interlayer water. Our results confirm that clay minerals, despite their well-known hygroscopic nature, have a significant hydrophobic character at the atomistic scale. The affinity of dissolved gases for the clay surface shows significant variations related to the size and shape of the adsorbing molecules and the structuring of interfacial water by clay surfaces. Our results indicate that dissolved gases likely do not behave as inert tracers in fine-grained sedimentary rocks such as shale and mudstone, as routinely assumed in groundwater hydrology studies. Our results have implications for the fundamental science of hydrophobic adsorption, for the use of dissolved gases as tracers of fluid migration in the subsurface, and for low-carbon energy technologies that rely on fine-grained sedimentary rocks, such as carbon capture and storage, nuclear energy, and the transition from coal to natural gas.

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“…Indeed, it provides no new insights on the magnitude of the solvation free energy μ̅* itself. According to eq , μ̅* can be obtained from u̅ V * and s̅ V * , these two quantities reflecting contributions from solute–solvent attractive interactions, solvent reorganization, and excluded-volume effects. , Hence, to further explore why the μ̅* values characteristic of hydrophobic hydration are positive, it seems reasonable to make use of theory and simulations aimed at gaining a deeper understanding of the origin of both u̅ V * and s̅ V * values at a microscopic level.…”

Section: Conclusion and Final Remarksmentioning

confidence: 99%

Water’s Thermal Pressure Drives the Temperature Dependence of Hydrophobic Hydration

Cerdeiriña

Debenedetti

2017

J. Phys. Chem. B

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With the aid of literature experimental data and reported results from molecular simulation, two thermodynamic relations are found to provide a theoretical basis for the understanding of a variety of characteristic features associated with the solvation of small nonpolar molecules in water. Thus, the large and positive solvation heat capacity, enthalpy-entropy compensation, the solubility minimum and solvation free energy maximum with respect to temperature, enthalpy convergence, and entropy convergence are rationalized in a unified way. Our key finding is that all of these phenomena are driven by the thermal pressure coefficient of pure water, which, via the isobaric thermal expansivity and the isothermal compressibility, reflects its unusual thermodynamics. Remarkably, the solubility minimum is found to be a direct consequence of water's density maximum.

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Shedding light on the hydrophobicity puzzle

Cited by 27 publications

References 60 publications

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

Hydrophobic Solvation of Gases (CO₂, CH₄, H₂, Noble Gases) in Clay Interlayer Nanopores

Water’s Thermal Pressure Drives the Temperature Dependence of Hydrophobic Hydration

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Shedding light on the hydrophobicity puzzle

Cited by 27 publications

References 60 publications

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

Molecular Interactions of Cephalosporins with the Deep Binding Pocket of the RND Transporter AcrB

Hydrophobic Solvation of Gases (CO2, CH4, H2, Noble Gases) in Clay Interlayer Nanopores

Water’s Thermal Pressure Drives the Temperature Dependence of Hydrophobic Hydration

Contact Info

Product

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Hydrophobic Solvation of Gases (CO₂, CH₄, H₂, Noble Gases) in Clay Interlayer Nanopores