7 research outputs found
On the Coupling between the Collective Dynamics of Proteins and Their Hydration Water
Picosecond time scale dynamics of hydrated proteins has been connected with the onset of biological activity as it coincides with solventâsolute hydrogen bond rearrangements and amino acid rotational relaxation time scales. The presence and fluctuations of protein hydration water (PHW) largely influence protein motions that are believed to be slaved to those of the solvent, yet to date, how protein and hydration water dynamics are coupled remains unclear. Here, we provide a significant advance in characterizing this coupling; we present the first full study of both the longitudinal and transverse coherent collective motions in a proteinâsolvent system. The data show unexpectedly the presence in the water dynamics of collective modes belonging to the protein. The properties of these modes, in particular, their propagation velocities and amplitudes, indicate a strengthening of the interactions and a higher rigidity of the network of solvent molecules close to the protein surface. Accordingly, the present study presents the most compelling and clear evidence of a very strong dynamical coupling between a protein and its hydration water, previously suggested by studies using various experimental techniques
Electrochemical Surface Potential Due to Classical Point Charge Models Drives Anion Adsorption to the AirâWater Interface
We demonstrate that the driving forces for ion adsorption
to the
airâwater interface for point charge models result from both
cavitation and a term that is of the form of a negative electrochemical
surface potential. We carefully characterize the role of the free
energy due to the <i>electrochemical</i> surface potential
computed from simple empirical models and its role in ionic adsorption
within the context of dielectric continuum theory. Our research suggests
that the electrochemical surface potential due to point charge models
provides anions with a significant driving force for adsoprtion to
the airâwater interface. This is contrary to the results of
ab initio simulations that indicate that the <i>average electrostatic</i> surface potential should favor the desorption of anions at the airâwater
interface. The results have profound implications for the studies
of ionic distributions in the vicinity of hydrophobic surfaces and
proteins
Specific Anion Effects on Na<sup>+</sup> Adsorption at the Aqueous SolutionâAir Interface: MD Simulations, SESSA Calculations, and Photoelectron Spectroscopy Experiments
Specific ion effects of the large
halide anions have been shown
to moderate anion adsorption to the airâwater interface (AWI),
but little quantitative attention has been paid to the behavior of
alkali cations. Here we investigate the concentration and local distribution
of sodium (Na<sup>+</sup>) at the AWI in dilute (<1 M) aqueous
solutions of NaCl, NaBr, and NaI using a combination of molecular
dynamics (MD) and SESSA simulations, and liquid jet ambient pressure
photoelectron spectroscopy measurements. We use SESSA to simulate
Na 2p photoelectron intensities on the basis of the atom density profiles
obtained from MD simulations, and we compare the simulation results
with photoelectron spectroscopy experiments to evaluate the performance
of a nonpolarizable force field model versus that of an induced dipole
polarizable one. Our results show that the nonpolarizable force model
developed by Horinek and co-workers (<i>Chem. Phys. Lett.</i> <b>2009</b>, <i>479</i>, 173â183) accurately
predicts the local concentration and distribution of Na<sup>+</sup> near the AWI for all three electrolytes, whereas the polarizable
model does not. To our knowledge, this is the first interface-specific
spectroscopic validation of a MD force field. The molecular origins
of the unique Na<sup>+</sup> distributions for the three electrolytes
are analyzed on the basis of electrostatic arguments, and shown to
arise from an indirect anion effect wherein the identity of the anion
affects the strength of the attractive Na<sup>+</sup>âH<sub>2</sub>O electrostatic interaction. Finally, we use the photoelectron
spectroscopy results to constrain the range of inelastic mean free
paths (IMFPs) for the three electrolyte solutions used in the SESSA
simulations that are able to reproduce the experimental intensities.
Our results suggest that earlier estimates of IMFPs for aqueous solutions
are likely too high
Multi-Conformation Monte Carlo: A Method for Introducing Flexibility in Efficient Simulations of Many-Protein Systems
We
present a novel multi-conformation Monte Carlo simulation method
that enables the modeling of proteinâprotein interactions and
aggregation in crowded protein solutions. This approach is relevant
to a molecular-scale description of realistic biological environments,
including the cytoplasm and the extracellular matrix, which are characterized
by high concentrations of biomolecular solutes (e.g., 300â400
mg/mL for proteins and nucleic acids in the cytoplasm of Escherichia coli). Simulation of such environments
necessitates the inclusion of a large number of protein molecules.
Therefore, computationally inexpensive methods, such as rigid-body
Brownian dynamics (BD) or Monte Carlo simulations, can be particularly
useful. However, as we demonstrate herein, the rigid-body representation
typically employed in simulations of many-protein systems gives rise
to certain artifacts in proteinâprotein interactions. Our approach
allows us to incorporate molecular flexibility in Monte Carlo simulations
at low computational cost, thereby eliminating ambiguities arising
from structure selection in rigid-body simulations. We benchmark and
validate the methodology using simulations of hen egg white lysozyme
in solution, a well-studied system for which extensive experimental
data, including osmotic second virial coefficients, small-angle scattering
structure factors, and multiple structures determined by X-ray and
neutron crystallography and solution NMR, as well as rigid-body BD
simulation results, are available for comparison
Watching the Low-Frequency Motions in Aqueous Salt Solutions: The Terahertz Vibrational Signatures of Hydrated Ions
The details of ion hydration still raise fundamental
questions
relevant to a large variety of problems in chemistry and biology.
The concept of water âstructure breakingâ and âstructure
makingâ by ions in aqueous solutions has been invoked to explain
the Hofmeister series introduced over 100 years ago, which still provides
the basis for the interpretation of experimental observations, in
particular the stabilization/destabilization of biomolecules. Recent
studies, using state-of-the-art experiments and molecular dynamics
simulations, either challenge or support some key points of the structure
maker/breaker concept, specifically regarding long-ranged ordering/disordering
effects. Here, we report a systematic terahertz absorption spectroscopy
and molecular dynamics simulation study of a series of aqueous solutions
of divalent salts, which adds a new piece to the puzzle. The picture
that emerges from the concentration dependence and assignment of the
observed absorption features is one of a limited range of ion effects
that is confined to the first solvation shell
Direct Evidence of Conformational Changes Associated with Voltage Gating in a Voltage Sensor Protein by Time-Resolved Xâray/Neutron Interferometry
The
voltage sensor domain (VSD) of voltage-gated cation (e.g.,
Na<sup>+</sup>, K<sup>+</sup>) channels central to neurological signal
transmission can function as a distinct module. When linked to an
otherwise voltage-insensitive, ion-selective membrane pore, the VSD
imparts voltage sensitivity to the channel. Proteins homologous with
the VSD have recently been found to function themselves as voltage-gated
proton channels or to impart voltage sensitivity to enzymes. Determining
the conformational changes associated with voltage gating in the VSD
itself in the absence of a pore domain thereby gains importance. We
report the direct measurement of changes in the scattering-length
density (SLD) profile of the VSD protein, vectorially oriented within
a reconstituted phospholipid bilayer membrane, as a function of the
transmembrane electric potential by time-resolved X-ray and neutron
interferometry. The changes in the experimental SLD profiles for both
polarizing and depolarizing potentials with respect to zero potential
were found to extend over the entire length of the isolated VSDâs
profile structure. The characteristics of the changes observed were
in qualitative agreement with molecular dynamics simulations of a
related membrane system, suggesting an initial interpretation of these
changes in terms of the VSDâs atomic-level 3-D structure
âBind and Crawlâ Association Mechanism of <i>Leishmania major</i> Peroxidase and Cytochrome <i>c</i> Revealed by Brownian and Molecular Dynamics Simulations
<i>Leishmania major</i>, the parasitic causative agent
of leishmaniasis, produces a heme peroxidase (LmP), which catalyzes
the peroxidation of mitochondrial cytochrome <i>c</i> (LmCytc)
for protection from reactive oxygen species produced by the host.
The association of LmP and LmCytc, which is known from kinetics measurements
to be very fast (âŒ10<sup>8</sup> M<sup>â1</sup> s<sup>â1</sup>), does not involve major conformational changes and
has been suggested to be dominated by electrostatic interactions.
We used Brownian dynamics simulations to investigate the mechanism
of formation of the LmPâLmCytc complex. Our simulations confirm
the importance of electrostatic interactions involving the negatively
charged D211 residue at the LmP active site, and reveal a previously
unrecognized role in complex formation for negatively charged residues
in helix A of LmP. The crystal structure of the D211N mutant of LmP
reported herein is essentially identical to that of wild-type LmP,
reinforcing the notion that it is the loss of charge at the active
site, and not a change in structure, that reduces the association
rate of the D211N variant of LmP. The Brownian dynamics simulations
further show that complex formation occurs via a âbind and
crawlâ mechanism, in which LmCytc first docks to a location
on helix A that is far from the active site, forming an initial encounter
complex, and then moves along helix A to the active site. An atomistic
molecular dynamics simulation confirms the helix A binding site, and
steady state activity assays and stopped-flow kinetics measurements
confirm the role of helix A charges in the association mechanism