A quantum chemical treatment of solvation effects using the standard quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations is challenging due to QM and MM solvent exchange ...near the QM solute. To this end, various adaptive QM/MM methods have been proposed; free solvent exchanges are allowed via flexible switching of their identities between QM and MM systems depending on their distances from the QM solute. However, temporal and spatial discontinuities remain in the standard implementations of adaptive QM/MM approaches and continue to hamper stable and accurate dynamics simulations. We previously demonstrated that the size-consistent multipartitioning (SCMP) method achieves temporal continuity while, to some extent, avoiding spatial discontinuities. In the present study, we demonstrate that residual spatial discontinuities may lead to severe artifacts under certain conditions. Through quantitative analyses, we show that all multiscale including QM/MM methods might experience these problems, which so far have not been investigated in depth. To alleviate these artifacts, we propose a correction scheme in the framework of the SCMP approach and demonstrate its effectiveness using bulk water simulations.
In MtrF, an outer-membrane multiheme cytochrome, the 10 heme groups are arranged in heme binding domains II and IV along the pseudo-C₂ axis, forming the electron transfer (ET) pathways. Previous ...reports based on molecular dynamics simulations showed that the redox potential (E
m) values for the heme pairs located in symmetrical positions in domains II and IV were similar, forming bidirectional ET pathways Breuer M, Zarzycki P, Blumberger J, Rosso KM (2012) J Am Chem Soc 134(24):9868–9871. Here, we present the E
m values of the 10 hemes in MtrF, solving the linear Poisson–Boltzmann equation and considering the protonation states of all titratable residues and heme propionic groups. In contrast to previous studies, the E
m values indicated that the ET is more likely to be downhill from domain IV to II because of localization of acidic residues in domain IV. Reduction of hemes in MtrF lowered the E
m values, resulting in switching to alternative downhill ET pathways that extended to the flavin binding sites. These findings present an explanation of how MtrF serves as an electron donor to extracellular substrates.
The cyanobacterial photosystem II (PSII) crystal structure includes more than 1300 water molecules in each monomer unit; however, their precise roles in water oxidation are unclear. To understand the ...origins of water molecules in the PSII crystal structure, the accessibility of bulk water molecules to channel inner spaces in PSII was investigated using the water-removed PSII structure and molecular dynamics (MD) simulations. The inner space of the channel that proceeds toward the D1-Glu65/D2-Glu312 pair (E65/E312 channel) was entirely filled with water molecules from the bulk region. In the same channel, a diamond-shaped cluster of water molecules formed near redox-active TyrZ in MD simulations. Reorientation of the D2-Leu352 side chain resulted in formation of a hexagonal water network at the Cl–2 binding site. Water molecules could not enter the main region of the O4–water chain, which proceeds from the O4 site of the Mn4CaO5 cluster. However, in the O4–water chain, the two water binding sites that are most distant from the protein bulk surface were occupied by water molecules that approached along the E65/E312 channel, one of which formed an H-bond with the O4 site. These findings provide key insights into the significance of the channel ends, which may utilize water molecules during the PSII photocycle.
For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) ...techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.
Abstract
A quantum chemistry study of the first singlet (
S
1
) and triplet (
T
1
) excited states of phenylsulfonyl-carbazole compounds, proposed as useful thermally activated delayed fluorescence ...(TADF) emitters for organic light emitting diode (OLED) applications, was performed with the quantum Equation-Of-Motion Variational Quantum Eigensolver (qEOM-VQE) and Variational Quantum Deflation (VQD) algorithms on quantum simulators and devices. These quantum simulations were performed with double zeta quality basis sets on an active space comprising the highest occupied and lowest unoccupied molecular orbitals (HOMO, LUMO) of the TADF molecules. The differences in energy separations between
S
1
and
T
1
(Δ
E
S
T
) predicted by calculations on quantum simulators were found to be in excellent agreement with experimental data. Differences of 17 and 88 mHa with respect to exact energies were found for excited states by using the qEOM-VQE and VQD algorithms, respectively, to perform simulations on quantum devices without error mitigation. By utilizing state tomography to purify the quantum states and correct energy values, the large errors found for unmitigated results could be improved to differences of, at most, 4 mHa with respect to exact values. Consequently, excellent agreement could be found between values of Δ
E
S
T
predicted by quantum simulations and those found in experiments.
In the cyanobacterial photosystem II (PSII), the O4-water chain in the D1 and CP43 proteins, a chain of water molecules that are directly H-bonded to O4 of the Mn
4
Ca cluster, is linked with a ...channel that connects the protein bulk surface along with a membrane-extrinsic protein subunit, PsbU (O4-PsbU channel). The cyanobacterial PSII structure also shows that the O1 site of the Mn
4
Ca cluster has a chain of H-bonded water molecules, which is linked with the channel that proceeds toward the bulk surface via PsbU and PsbV (O1-PsbU/V channel). Membrane-extrinsic protein subunits PsbU and PsbV in cyanobacterial PSII are replaced with PsbP and PsbQ in plant PSII. However, these four proteins have no structural similarity. It remains unknown whether the corresponding channels also exist in plant PSII, because water molecules are not identified in the plant PSII cryo-electron microscopy (cryo-EM) structure. Using the cyanobacterial and plant PSII structures, we analyzed the channels that proceed from the Mn
4
Ca cluster. The cyanobacterial O4-PsbU and O1-PsbU/V channels were structurally conserved as the channel that proceeds along PsbP toward the protein bulk surface in the plant PSII (O4-PsbP and O1-PsbP channels, respectively). Calculated protonation states indicated that in contrast to the original geometry of the plant cryo-EM structure, protonated PsbP-Lys166 may form a salt-bridge with ionized D1-Glu329 and protonated PsbP-Lys173 may form a salt-bridge with ionized PsbQ-Asp28 near the O1-PsbP channel. The existence of these channels might explain the molecular mechanism of how PsbP can interact with the Mn
4
Ca cluster.
We propose a new adaptive QM/MM method, the size-consistent multipartitioning (SCMP) QM/MM scheme, which enables stable and computationally efficient QM/MM simulations. A number of partitionings with ...identical size of the QM and the MM regions are considered with a new adaptive scheme in order to (1) realize smooth QM/MM switching, (2) introduce a conserved quantity (total energy, Hamiltonian), (3) avoid spurious artificial forces on the QM/MM border, and (4) allow for an efficient parallel implementation. Benchmark simulations performed for “QM water in MM water” show that energy conservation can be significantly improved and the computational efficiency allows treating also larger QM regions, for which previous methods had to face an intractable increase in computer time.
REPLY TO BREUER ET AL Watanabe, Hiroshi C.; Yamashita, Yuki; Ishikita, Hiroshi
Proceedings of the National Academy of Sciences - PNAS,
11/2017, Volume:
114, Issue:
47
Journal Article
Channelrhodopsins (ChRs) are light-gated cation channels that mediate ion transport across membranes in microalgae (vectorial catalysis). ChRs gain increasing attention as useful tools for the ...analysis of neural networks in tissues and living animals (optogenetics). In fact, various mutagenesis approaches have realized practical applications with high reliability by enhancement of the expression level, channel kinetics control, and color tuning. Furthermore, the recently published x-ray structure has provided valuable information for further atomistic studies and engineering ChRs for a wider application. The present study is a computational attempt to describe the functional mechanism at the atomic level based on the x-ray structure. We present several structural characteristics that are highly involved in ion channel gating and ion transport, including (1) water distribution, (2) cation binding sites, (3) intrahelical hydrogen bond, (4) DC gate, and (5) active site.
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► The x-ray structure of ChR, as well as its application in optogenetics, was recently released. ► Based on the x-ray structure, the structure of ChR2 is modeled and simulated. ► Various structural properties involved in the channel function are revealed. ► The first atomic level understanding promotes the engineering of applications.
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