Matching Items (14)

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Dielectric constant of water in the interface

Description

We define the dielectric constant (susceptibility) that should enter the Maxwell boundary value problem when applied to microscopic dielectric interfaces polarized by external fields. The dielectric constant (susceptibility) of the

We define the dielectric constant (susceptibility) that should enter the Maxwell boundary value problem when applied to microscopic dielectric interfaces polarized by external fields. The dielectric constant (susceptibility) of the interface is defined by exact linear-response equations involving correlations of statistically fluctuating interface polarization and the Coulomb interaction energy of external charges with the dielectric. The theory is applied to the interface between water and spherical solutes of altering size studied by molecular dynamics (MD) simulations. The effective dielectric constant of interfacial water is found to be significantly lower than its bulk value, and it also depends on the solute size. For TIP3P water used in MD simulations, the interface dielectric constant changes from 9 to 4 when the solute radius is increased from ∼5 to 18 Å.

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Date Created
  • 2016-07-06

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Configurational entropy of polar glass formers and the effect of electric field on glass transition

Description

A model of low-temperature polar liquids is constructed that accounts for the configurational heat capacity, entropy, and the effect of a strong electric field on the glass transition. The model

A model of low-temperature polar liquids is constructed that accounts for the configurational heat capacity, entropy, and the effect of a strong electric field on the glass transition. The model is based on the Padé-truncated perturbation expansions of the liquid state theory. Depending on parameters, it accommodates an ideal glass transition of vanishing configurational entropy and its avoidance, with a square-root divergent enumeration function at the point of its termination. A composite density-temperature parameter ρ[superscript γ]/T, often used to represent combined pressure and temperature data, follows from the model. The theory is in good agreement with the experimental data for excess (over the crystal state) thermodynamics of molecular glass formers. We suggest that the Kauzmann entropy crisis might be a signature of vanishing configurational entropy of a subset of degrees of freedom, multipolar rotations in our model. This scenario has observable consequences: (i) a dynamical crossover of the relaxation time and (ii) the fragility index defined by the ratio of the excess heat capacity and excess entropy at the glass transition. The Kauzmann temperature of vanishing configurational entropy and the corresponding glass transition temperature shift upward when the electric field is applied. The temperature shift scales quadratically with the field strength.

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Created

Date Created
  • 2016-07-20

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Electron-transfer chain in respiratory complex I

Description

Complex I is a part of the respiration energy chain converting the redox energy into the cross-membrane proton gradient. The electron-transfer chain of iron-sulfur cofactors within the water-soluble peripheral part

Complex I is a part of the respiration energy chain converting the redox energy into the cross-membrane proton gradient. The electron-transfer chain of iron-sulfur cofactors within the water-soluble peripheral part of the complex is responsible for the delivery of electrons to the proton pumping subunit. The protein is porous to water penetration and the hydration level of the cofactors changes when the electron is transferred along the chain. High reaction barriers and trapping of the electrons at the iron-sulfur cofactors are prevented by the combination of intense electrostatic noise produced by the protein-water interface with the high density of quantum states in the iron-sulfur clusters caused by spin interactions between paramagnetic iron atoms. The combination of these factors substantially lowers the activation barrier for electron transfer compared to the prediction of the Marcus theory, bringing the rate to the experimentally established range. The unique role of iron-sulfur clusters as electron-transfer cofactors is in merging protein-water fluctuations with quantum-state multiplicity to allow low activation barriers and robust operation. Water plays a vital role in electron transport energetics by electrowetting the cofactors in the chain upon arrival of the electron. A general property of a protein is to violate the fluctuation-dissipation relation through nonergodic sampling of its landscape. High functional efficiency of redox enzymes is a direct consequence of nonergodicity.

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Created

Date Created
  • 2017-07-14

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Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

Description

Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower

Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work.

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Date Created
  • 2016-06-16

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Quantifying Solvent Kinetics in Molecular Dynamics Simulations of Biomolecules

Description

The relation between water and protein physics is a topic of much interest. Molecular dynamics (MD) simulations of biomolecules are a common computational technique to obtain atomistic insight into the

The relation between water and protein physics is a topic of much interest. Molecular dynamics (MD) simulations of biomolecules are a common computational technique to obtain atomistic insight into the physical behavior of biomolecules, including the nature of the interaction between water and the protein. In order to model biomolecules at the highest level of accuracy, an explicit, atomistic representation of the water is typically necessary. The number of water molecules that need to be simulated is normally on the order of thousands. The high dimensional MD dataset is then expanded with considerably more dimensions. We describe here a set of tools which can be used to extract general features of the water behavior, which can then be utilized to build simplified models of the water kinetics which make quantitative predictions, such as the flux rate through a pore.

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Date Created
  • 2015-12

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Non-Gaussian Lineshapes and Dynamics of Time-Resolved Linear and Nonlinear (Correlation) Spectra

Description

Signatures of nonlinear and non-Gaussian dynamics in time-resolved linear and nonlinear (correlation) 2D spectra are analyzed in a model considering a linear plus quadratic dependence of the spectroscopic transition frequency

Signatures of nonlinear and non-Gaussian dynamics in time-resolved linear and nonlinear (correlation) 2D spectra are analyzed in a model considering a linear plus quadratic dependence of the spectroscopic transition frequency on a Gaussian nuclear coordinate of the thermal bath (quadratic coupling). This new model is contrasted to the commonly assumed linear dependence of the transition frequency on the medium nuclear coordinates (linear coupling). The linear coupling model predicts equality between the Stokes shift and equilibrium correlation functions of the transition frequency and time-independent spectral width. Both predictions are often violated, and we are asking here the question of whether a nonlinear solvent response and/or non-Gaussian dynamics are required to explain these observations. We find that correlation functions of spectroscopic observables calculated in the quadratic coupling model depend on the chromophore’s electronic state and the spectral width gains time dependence, all in violation of the predictions of the linear coupling models. Lineshape functions of 2D spectra are derived assuming Ornstein–Uhlenbeck dynamics of the bath nuclear modes. The model predicts asymmetry of 2D correlation plots and bending of the center line. The latter is often used to extract two-point correlation functions from 2D spectra. The dynamics of the transition frequency are non-Gaussian. However, the effect of non-Gaussian dynamics is limited to the third-order (skewness) time correlation function, without affecting the time correlation functions of higher order. The theory is tested against molecular dynamics simulations of a model polar–polarizable chromophore dissolved in a force field water.

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Created

Date Created
  • 2014-07-17

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Protein electron transfer: Dynamics and statistics

Description

Electron transfer between redox proteins participating in energy chains of biology is required to proceed with high energetic efficiency, minimizing losses of redox energy to heat. Within the standard models

Electron transfer between redox proteins participating in energy chains of biology is required to proceed with high energetic efficiency, minimizing losses of redox energy to heat. Within the standard models of electron transfer, this requirement, combined with the need for unidirectional (preferably activationless) transitions, is translated into the need to minimize the reorganization energy of electron transfer. This design program is, however, unrealistic for proteins whose active sites are typically positioned close to the polar and flexible protein-water interface to allow inter-protein electron tunneling. The high flexibility of the interfacial region makes both the hydration water and the surface protein layer act as highly polar solvents. The reorganization energy, as measured by fluctuations, is not minimized, but rather maximized in this region. Natural systems in fact utilize the broad breadth of interfacial electrostatic fluctuations, but in the ways not anticipated by the standard models based on equilibrium thermodynamics. The combination of the broad spectrum of static fluctuations with their dispersive dynamics offers the mechanism of dynamical freezing (ergodicity breaking) of subsets of nuclear modes on the time of reaction/residence of the electron at a redox cofactor. The separation of time-scales of nuclear modes coupled to electron transfer allows dynamical freezing. In particular, the separation between the relaxation time of electro-elastic fluctuations of the interface and the time of conformational transitions of the protein caused by changing redox state results in dynamical freezing of the latter for sufficiently fast electron transfer. The observable consequence of this dynamical freezing is significantly different reorganization energies describing the curvature at the bottom of electron-transfer free energy surfaces (large) and the distance between their minima (Stokes shift, small). The ratio of the two reorganization energies establishes the parameter by which the energetic efficiency of protein electron transfer is increased relative to the standard expectations, thus minimizing losses of energy to heat. Energetically efficient electron transfer occurs in a chain of conformationally quenched cofactors and is characterized by flattened free energy surfaces, reminiscent of the flat and rugged landscape at the stability basin of a folded protein.

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Date Created
  • 2013

Single-Focus Confocal Data Analysis with Bayesian Nonparametrics

Description

The cell is a dense environment composes of proteins, nucleic acids, as well as other small molecules, which are constantly bombarding each other and interacting. These interactions and the diffusive

The cell is a dense environment composes of proteins, nucleic acids, as well as other small molecules, which are constantly bombarding each other and interacting. These interactions and the diffusive motions are driven by internal thermal fluctuations. Upon collision, molecules can interact and form complexes. It is of interest to learn kinetic parameters such as reaction rates of one molecule converting to different species or two molecules colliding and form a new species as well as to learn diffusion coefficients.

Several experimental measurements can probe diffusion coefficients at the single-molecule and bulk level. The target of this thesis is on single-molecule methods, which can assess diffusion coefficients at the individual molecular level. For instance, super resolution methods like stochastic optical reconstruction microscopy (STORM) and photo activated localization microscopy (PALM), have a high spatial resolution with the cost of lower temporal resolution. Also, there is a different group of methods, such as MINFLUX, multi-detector tracking, which can track a single molecule with high spatio-temporal resolution. The problem with these methods is that they are only applicable to very diluted samples since they need to ensure existence of a single molecule in the region of interest (ROI).

In this thesis, the goal is to have the best of both worlds by achieving high spatio-temporal resolutions without being limited to a few molecules. To do so, one needs to refocus on fluorescence correlation spectroscopy (FCS) as a method that applies to both in vivo and in vitro systems with a high temporal resolution and relies on multiple molecules traversing a confocal volume for an extended period of time. The difficulty here is that the interpretation of the signal leads to different estimates for the kinetic parameters such as diffusion coefficients based on a different number of molecules we consider in the model. It is for this reason that the focus of this thesis is now on using Bayesian nonparametrics (BNPs) as a way to solve this model selection problem and extract kinetic parameters such as diffusion coefficients at the single-molecule level from a few photons, and thus with the highest temporal resolution as possible.

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Agent

Created

Date Created
  • 2020

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The Pauli-Lubanski Vector in a Group-Theoretical Approach to Relativistic Wave Equations

Description

Chapter 1 introduces some key elements of important topics such as; quantum mechanics,

representation theory of the Lorentz and Poincare groups, and a review of some basic rela- ´

tivistic wave equations

Chapter 1 introduces some key elements of important topics such as; quantum mechanics,

representation theory of the Lorentz and Poincare groups, and a review of some basic rela- ´

tivistic wave equations that will play an important role in the work to follow. In Chapter 2,

a complex covariant form of the classical Maxwell’s equations in a moving medium or at

rest is introduced. In addition, a compact, Lorentz invariant, form of the energy-momentum

tensor is derived. In chapter 3, the concept of photon helicity is critically analyzed and its

connection with the Pauli-Lubanski vector from the viewpoint of the complex electromag- ´

netic field, E+ iH. To this end, a complex covariant form of Maxwell’s equations is used.

Chapter 4 analyzes basic relativistic wave equations for the classical fields, such as Dirac’s

equation, Weyl’s two-component equation for massless neutrinos and the Proca, Maxwell

and Fierz-Pauli equations, from the viewpoint of the Pauli-Lubanski vector and the Casimir ´

operators of the Poincare group. A connection between the spin of a particle/field and ´

consistency of the corresponding overdetermined system is emphasized in the massless

case. Chapter 5 focuses on the so-called generalized quantum harmonic oscillator, which

is a Schrodinger equation with a time-varying quadratic Hamiltonian operator. The time ¨

evolution of exact wave functions of the generalized harmonic oscillators is determined

in terms of the solutions of certain Ermakov and Riccati-type systems. In addition, it is

shown that the classical Arnold transform is naturally connected with Ehrenfest’s theorem

for generalized harmonic oscillators. In Chapter 6, as an example of the usefulness of the

methods introduced in Chapter 5 a model for the quantization of an electromagnetic field

in a variable media is analyzed. The concept of quantization of an electromagnetic field

in factorizable media is discussed via the Caldirola-Kanai Hamiltonian. A single mode

of radiation for this model is used to find time-dependent photon amplitudes in relation

to Fock states. A multi-parameter family of the squeezed states, photon statistics, and the

uncertainty relation, are explicitly given in terms of the Ermakov-type system.

Contributors

Agent

Created

Date Created
  • 2016

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Applications of adaptive umbrella sampling in biomolecular simulation

Description

Conformational changes in biomolecules often take place on longer timescales than are easily accessible with unbiased molecular dynamics simulations, necessitating the use of enhanced sampling techniques, such as adaptive umbrella

Conformational changes in biomolecules often take place on longer timescales than are easily accessible with unbiased molecular dynamics simulations, necessitating the use of enhanced sampling techniques, such as adaptive umbrella sampling. In this technique, the conformational free energy is calculated in terms of a designated set of reaction coordinates. At the same time, estimates of this free energy are subtracted from the potential energy in order to remove free energy barriers and cause conformational changes to take place more rapidly. This dissertation presents applications of adaptive umbrella sampling to a variety of biomolecular systems. The first study investigated the effects of glycosylation in GalNAc2-MM1, an analog of glycosylated macrophage activating factor. It was found that glycosylation destabilizes the protein by increasing the solvent exposure of hydrophobic residues. The second study examined the role of bound calcium ions in promoting the isomerization of a cis peptide bond in the collagen-binding domain of Clostridium histolyticum collagenase. This study determined that the bound calcium ions reduced the barrier to the isomerization of this peptide bond as well as stabilizing the cis conformation thermodynamically, and identified some of the reasons for this. The third study represents the application of GAMUS (Gaussian mixture adaptive umbrella sampling) to on the conformational dynamics of the fluorescent dye Cy3 attached to the 5' end of DNA, and made predictions concerning the affinity of Cy3 for different base pairs, which were subsequently verified experimentally. Finally, the adaptive umbrella sampling method is extended to make use of the roll angle between adjacent base pairs as a reaction coordinate in order to examine the bending both of free DNA and of DNA bound to the archaeal protein Sac7d. It is found that when DNA bends significantly, cations from the surrounding solution congregate on the concave side, which increases the flexibility of the DNA by screening the repulsion between phosphate backbones. The flexibility of DNA on short length scales is compared to the worm-like chain model, and the contribution of cooperativity in DNA bending to protein-DNA binding is assessed.

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Created

Date Created
  • 2011