10 research outputs found
Adaptive-Partitioning QM/MM for Molecular Dynamics Simulations: 4. Proton Hopping in Bulk Water
By reclassifying atoms as QM or MM
on-the-fly, adaptive QM/MM dynamics
simulations can utilize small QM subsystems whose locations and contents
are continuously and automatically updated. Although adaptive QM/MM
has been applied in studies of a variety of ions, dynamics simulations
of a hydrated proton in bulk water remain a challenge. The difficulty
arises from the need to transfer structural features (the covalent
and hydrogen bonding networks) via the Grotthuss mechanism instead
of the given proton. One must therefore identify an appropriate reference
point from which the QM subsystem can be positioned that continuously
follows the structural variations as the proton hops. To solve this
problem, we propose a proton indicator that serves as the needed reference
point. The location of the proton indicator varies smoothly from the
hydronium oxygen in the resting (Eigen) state to the shared proton
in the transition (Zundel) state. The algorithm is implemented in
the framework of a modified permuted adaptive-partitioning QM/MM.
As a proof of concept, we simulate an excess proton solvated in bulk
water, where the QM subsystem is defined as a sphere of 4.0 Ă
radius centered at the proton indicator. We find that the use of the
proton indicator prevents abrupt changes in the location and contents
of the QM subsystem. The new method yields reasonably good agreement
in the proton solvation structure and in the proton transfer dynamics
with previously reported conventional QM/MM dynamics simulations that
employed a much larger QM subsystem (a sphere of 12 Ă
radius).
Also, the results do not change significantly with respect to variations
in the time step size (0.1 or 0.5 fs), truncation of the many-body
expansion of the potential (from fifth to second order), and absence/presence
of thermostat. The proton indicator combined with the modified permuted
adaptive-partitioning scheme thus appears to be a useful tool for
studying proton transfer in solution
Adaptive-Partitioning QM/MM for Molecular Dynamics Simulations: 4. Proton Hopping in Bulk Water
By reclassifying atoms as QM or MM
on-the-fly, adaptive QM/MM dynamics
simulations can utilize small QM subsystems whose locations and contents
are continuously and automatically updated. Although adaptive QM/MM
has been applied in studies of a variety of ions, dynamics simulations
of a hydrated proton in bulk water remain a challenge. The difficulty
arises from the need to transfer structural features (the covalent
and hydrogen bonding networks) via the Grotthuss mechanism instead
of the given proton. One must therefore identify an appropriate reference
point from which the QM subsystem can be positioned that continuously
follows the structural variations as the proton hops. To solve this
problem, we propose a proton indicator that serves as the needed reference
point. The location of the proton indicator varies smoothly from the
hydronium oxygen in the resting (Eigen) state to the shared proton
in the transition (Zundel) state. The algorithm is implemented in
the framework of a modified permuted adaptive-partitioning QM/MM.
As a proof of concept, we simulate an excess proton solvated in bulk
water, where the QM subsystem is defined as a sphere of 4.0 Ă
radius centered at the proton indicator. We find that the use of the
proton indicator prevents abrupt changes in the location and contents
of the QM subsystem. The new method yields reasonably good agreement
in the proton solvation structure and in the proton transfer dynamics
with previously reported conventional QM/MM dynamics simulations that
employed a much larger QM subsystem (a sphere of 12 Ă
radius).
Also, the results do not change significantly with respect to variations
in the time step size (0.1 or 0.5 fs), truncation of the many-body
expansion of the potential (from fifth to second order), and absence/presence
of thermostat. The proton indicator combined with the modified permuted
adaptive-partitioning scheme thus appears to be a useful tool for
studying proton transfer in solution
Adaptive-Partitioning QM/MM Dynamics Simulations: 3. Solvent Molecules Entering and Leaving Protein Binding Sites
The adaptive-partitioning
(AP) schemes for combined quantum-mechanical/molecular-mechanical
(QM/MM) calculations allow on-the-fly reclassifications of atoms and
molecules as QM or MM in dynamics simulations. The permuted-AP (PAP)
scheme (<i>J. Phys. Chem. B</i> <b>2007</b>, <i>111</i>, 2231) introduces a thin layer of buffer zone between
the QM subsystem (also called active zone) and the MM subsystem (also
known as the environmental zone) to provide a continuous and smooth
transition and expresses the potential energy in a many-body expansion
manner. The PAP scheme has been successfully applied to study small
molecules solvated in bulk solvent. Here, we propose two modifications
to the original PAP scheme to treat solvent molecules entering and
leaving protein binding sites. First, the center of the active zone
is placed at a pseudoatom in the binding site, whose position is not
affected by the movements of ligand or residues in the binding site.
Second, the extra forces due to the smoothing functions are deleted.
The modified PAP scheme no longer describes a Hamiltonian system,
but it satisfies the conservation of momentum. As a proof-of-concept
experiment, the modified PAP scheme is applied to the simulations
under the canonical ensemble for two binding sites of the <i>Escherichia coli</i> CLC chloride ion transport protein, in
particular, the intracellular binding site S<sub>int</sub> discovered
by crystallography and one putative additional binding site S<sub>add</sub> suggested by molecular modeling. The exchange of water
molecules between the binding sites and bulk solvent is monitored.
For comparison, simulations are also carried out using the same model
system and setup with only one exception: the extra forces due to
the smoothing functions are retained. The simulations are benchmarked
against conventional QM/MM simulations with large QM subsystems. The
results demonstrate that the active zone centered at the pseudo atom
is a reasonable and convenient representation of the binding site.
Moreover, the transient extra forces are non-negligible and cause
the QM water molecules to move out of the active zone. The modified
PAP scheme, where the extra forces are excluded, avoids the artifact,
providing a realistic description of the exchange of water molecules
between the protein binding sites and bulk solvent
Charge Transfer and Polarization for Chloride Ions Bound in ClC Transport Proteins: Natural Bond Orbital and Energy Decomposition Analyses
ClC
transport proteins show a distinct âbroken-helixâ
architecture, in which certain Îą-helices are oriented with their
N-terminal ends pointed toward the binding sites where the chloride
ions are held extensively by the backbone amide nitrogen atoms from
the helices. To understand the effectiveness of such binding structures,
we carried out natural bond orbital analysis and energy decomposition
analysis employing truncated active-site model systems for the bound
chloride ions along the translocation pore of the EcClC proteins.
Our results indicated that the chloride ions are stabilized in such
a binding environment by electrostatic, polarization, and charge-transfer
interactions with the backbone and a few side chains. Up to âź25%
of the formal charges of the chloride ions were found smeared out
to the surroundings primarily via charge transfer from the chlorideâs
lone pair <i>n</i>(Cl) orbitals to the proteinâs
antibonding Ď*Â(NâH) or Ď*Â(OâH) orbitals;
those Ď* orbitals are localized at the polar NâH and
OâH bonds in the chlorideâs first solvation shells formed
by the backbone amide groups and the side chains of residues Ser107,
Arg147, Glu148, and Tyr445. Polarizations by the chloride ions were
dominated by the redistribution of charge densities among the Ď
orbitals and lone pair orbitals of the protein atoms, in particular
the atoms of the backbone peptide links and of the side chains of
Arg147, Glu148, and Tyr445. The substantial amounts of electron density
involved in charge transfer and in polarization were consistent with
the large energetic contributions by the two processes revealed by
the energy decomposition analysis. The significant polarization and
charge-transfer effects may have impacts on the mechanisms and dynamics
of the chloride transport by the ClC proteins