Non‐Debye frustrated hydration steers biomolecular association: interfacial tension for the drug designer

Fernández, Ariel

doi:10.1002/1873-3468.12418

Cited by 4 publications

(7 citation statements)

References 34 publications

(75 reference statements)

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“…Adopting a higher level of generality, we also include the orthogonal polarization component

{bold-italicP}^{#}

in the dielectric picture. Since this component arises from the uncompensated partial charges resulting from frustration, it follows the structural distortion of the water hydrogen‐bond network, thus fulfilling the experimentally validated relation

P^{#} = - ξ bold-italic \nabla ϕ

, where

ξ = {(ω ε_{0})}^{1 / 2}

and

ω = 9.18 \times 10^{- 20} m J Å^{- 1}

. Thus, the uncompensated charge

γ^{#}

induced by frustration is determined by the curvature of

ϕ : γ^{#} = - bold-italic \nabla . P^{#} = ξ \nabla^{2} ϕ

, and the following relation holds:

P^{| |} = P - P^{#} = P + ξ bold-italic \nabla ϕ

.…”

Section: Theorymentioning

confidence: 88%

“…The Green function

G^{| |} false(t false)

becomes readily accessible from the fluctuation‐dissipation computation :

χ_{0}^{| |} ε_{0} G^{| |} (t) = - \frac{β}{2} \partial / \partial t 〈p^{| |} (0) . P^{| |} (t)〉,

where “< >” indicates the average over trajectories in phase space,

β = {(k_{B} T)}^{- 1}

and

bold-italicp^{false| false|}

= denotes parallel polarization density.…”

Section: Theorymentioning

confidence: 99%

“…Thus, a nanoscale theory of water dielectrics has been long overdue. Recent work revealed that the nanoscale behavior is attributable in good measure to water frustration . Accordingly, this work introduces a frustration‐related non‐Debye polarization term to account for the nanoscale dielectric response.…”

Section: Introductionmentioning

confidence: 99%

“…Frustration, described by the scalar field

ϕ = ϕ (r)

, refers to the reduction in the expected number of hydrogen‐bond coordinations of a water molecule with the oxygen atom placed within a ball centered at position r . The dynamic nature of liquid water and the limitations of the force fields adopted to reproduce this behavior prompts us to average over relaxation time intervals (τ ≈ 10 ps) and space (ball radius B fixed at 4 Å) to generate a scalar field of expected values.…”

Section: Introductionmentioning

confidence: 99%

“…The dynamic nature of liquid water and the limitations of the force fields adopted to reproduce this behavior prompts us to average over relaxation time intervals (τ ≈ 10 ps) and space (ball radius B fixed at 4 Å) to generate a scalar field of expected values. These values are less informative that instant fine grained snapshots but more reliable given dynamic and orientation uncertainty at sub‐picosecond levels and single position . Furthermore, the discrete nature of water hydrogen bond patterns clashes with the differentiability demanded by semiclassical electrostatic treatments, so the averaging is required to smooth out the scalar field.…”

Section: Introductionmentioning

confidence: 99%

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Dielectric response of frustrated water down to a single‐molecule contribution

Fernández¹

2017

Annalen der Physik

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A theory of dielectric response of water under nanoscale confinement was long overdue. This work addresses the problem by establishing a relation between dielectric response and hydrogen-bond frustration subsumed in a non-Debye polarization term. The results hold down to the single-molecule contribution and are validated vis-à-vis experimental measurements on a system where dielectric modulation entails removal of a single water molecule. The frustrated dielectric response down to molecular scales is assessed by contrasting two enantiomeric ligands in association with the same protein, with the complexes differing in the removal of a single interfacial water molecule.

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“…Adopting a higher level of generality, we also include the orthogonal polarization component