An Efficient Linear-Scaling Electrostatic Coupling for Treating Periodic Boundary Conditions in QM/MM Simulations

Laino, Teodoro; Mohamed, Fawzi; Laio, Alessandro; Parrinello, Michele

doi:10.1021/ct6001169

Cited by 159 publications

(162 citation statements)

References 63 publications

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“…The electron density was expanded by auxiliary plane wave basis set up to 360 Ry. The Gaussian expansion of the electrostatic potential scheme was used to treat the QM/MM electrostatic coupling with periodic boundary conditions (79,80), and the spurious QM/QM periodic image interactions were decoupled as described in ref. 81.…”

Section: Methods and Simulation Detailsmentioning

confidence: 99%

Acid activation mechanism of the influenza A M2 proton channel

Liang

Swanson

Madsen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

146

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The homotetrameric influenza A M2 channel (AM2) is an acidactivated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.ion channel | proton conduction | multiscale modeling | QM/MM | free-energy sampling V isualizing the vectorial flow of protons through membrane proteins is a long-standing challenge in biophysics and chemistry, with manifold implications for understanding bioenergetics, active transport, and proton channel function. Multiscale modeling has become a full partner with experimental structural biology in addressing proton transport (PT), because it can connect the dots between the high-resolution but static pictures obtained from crystallography and the lower-resolution but dynamically informed structures seen in the ensemble averages by NMR and other spectroscopic approaches. In general, multiscale modeling connects three or more disparate but coupled scales of behavior. In the case of PT in proteins, there are usually four pertinent scales: (i) the quantum mechanical scale of bond breaking and bond making inherent in the Grotthuss proton shuttle mechanism; (ii) the molecular scale of the dynamical motions of the protein, membrane, ions, and water molecules; (iii) the "free energy" scale that arises from the statistical ensemble averaging of those molecular motions; and (iv) the "transport" scale that manifests as a macroscopic conductance, with associated gating and other possible behaviors tied to macroscopic experimental variables. The proper and rigorous connection of these various scales, in an overall multiscale computational simulation, is often a substantial challenge. Here, we turn our attention to understanding the me...

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Section: Methods and Simulation Detailsmentioning

confidence: 99%

Acid activation mechanism of the influenza A M2 proton channel

Liang

Swanson

Madsen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

146

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“…In this Letter, water-gated charge transport is elucidated at the molecular level by performing self-interaction corrected [23] density-functional quantum mechanical and molecular mechanical [24,25] (SIC-QM/MM) computations using two models of the A:T bridge in explicit water solvent. The first, termed ''ideal,'' is the experimentally averaged x-ray structure of Arnott B-DNA.…”

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confidence: 99%

“…1 and reference [23]). The remaining energy terms describing the molecular mechanical system and the coupling between QM and MM regions are standard [24,25]. Other computational details are given elsewhere [33][34][35].…”

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confidence: 99%

Solvent Effects on Charge Spatial Extent in DNA and Implications for Transfer

et al. 2007

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To clarify the role played by water in facilitating long-range DNA charge transport, carefully designed, state-of-the-art, self-interaction corrected density-functional quantum mechanical and molecular mechanical (SIC-QM/MM) simulations are performed for the first time on two ionized adenine:thymine bridge models in explicit water solvent at finite temperature. For random solvent configurations, the charge is partially delocalized. However, a charge localization on different, well-separated adenines can be induced and is correlated with a restructuring of their first solvation shells. Thus, the importance of water in the mechanism of long-range charge transport is explicitly demonstrated, and the microscopic conditions for a charge localization are revealed.

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“…For the present calculation, we have used a QM/MM scheme previously tested and applied on α-quartz [54][55][56]. The MM α-quartz crystal is made of 15552 atoms in an orthorhombic cell with lattice constants of 49.94, 57.66, and 63.49Å, and is described using the van Beest-Kramer-van Santen (BKS) potential [57].…”

Section: Nmrmentioning

confidence: 99%

Magnetic linear response properties calculations with the Gaussian and augmented-plane-wave method

Weber

Iannuzzi

Gianì

et al. 2009

The Journal of Chemical Physics

101

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We introduce a method for the all-electron calculation of the NMR chemical shifts and the EPR g tensor using the Gaussian and augmented-plane-wave method. The presented approach is based on the generalized density functional perturbation theory. The method is validated by comparison with other theoretical methods for a selection of small molecules. We also present two exemplary applications that involve the calculation of the chemical shifts of a hydrated adenine and the g tensor for the E-1(') center in alpha-quartz using a quantum mechanical/molecular mechanical approach. Magnetic linear response properties calculations with the AbstractWe introduce a method for the all-electron calculation of the NMR chemical shifts and the EPR g tensor using the Gaussian and augmented-plane-wave method. The presented approach is based on the generalized density functional perturbation theory. The method is validated by comparison with other theoretical methods for a selection of small molecules. We also present two exemplary applications which involve the calculation of the chemical shifts of a hydrated adenine and the g tensor for the E 1 center in α-quartz using a quantum mechanical/molecular mechanical approach. * Electronic address: vweber@pci.uzh.ch

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An Efficient Linear-Scaling Electrostatic Coupling for Treating Periodic Boundary Conditions in QM/MM Simulations

Cited by 159 publications

References 63 publications

Acid activation mechanism of the influenza A M2 proton channel

Acid activation mechanism of the influenza A M2 proton channel

Solvent Effects on Charge Spatial Extent in DNA and Implications for Transfer

Magnetic linear response properties calculations with the Gaussian and augmented-plane-wave method

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