Dynamics Of Molecules In Solution Research Articles

Computational Modeling of Molecular Structures Guided by Hydrogen-Exchange Data.

Data produced by hydrogen-exchange monitoring experiments have been used in structural studies of molecules for several decades. Despite uncertainties about the structural determinants of hydrogen exchange itself, such data have successfully helped guide the structural modeling of challenging molecular systems, such as membrane proteins or large macromolecular complexes. As hydrogen-exchange monitoring provides information on the dynamics of molecules in solution, it can complement other experimental techniques in so-called integrative modeling approaches. However, hydrogen-exchange data have often only been used to qualitatively assess molecular structures produced by computational modeling tools. In this paper, we look beyond qualitative approaches and survey the various paradigms under which hydrogen-exchange data have been used to quantitatively guide the computational modeling of molecular structures. Although numerous prediction models have been proposed to link molecular structure and hydrogen exchange, none of them has been widely accepted by the structural biology community. Here, we present as many hydrogen-exchange prediction models as we could find in the literature, with the aim of providing the first exhaustive list of its kind. From purely structure-based models to so-called fractional-population models or knowledge-based models, the field is quite vast. We aspire for this paper to become a resource for practitioners to gain a broader perspective on the field and guide research toward the definition of better prediction models. This will eventually improve synergies between hydrogen-exchange monitoring and molecular modeling.

How wide is the window opened by high-resolution relaxometry on the internal dynamics of proteins in solution?

The dynamics of molecules in solution is usually quantified by the determination of timescale-specific amplitudes of motions. High-resolution nuclear magnetic resonance (NMR) relaxometry experiments—where the sample is transferred to low fields for longitudinal (T1) relaxation, and back to high field for detection with residue-specific resolution—seeks to increase the ability to distinguish the contributions from motion on timescales slower than a few nanoseconds. However, tumbling of a molecule in solution masks some of these motions. Therefore, we investigate to what extent relaxometry improves timescale resolution, using the “detector” analysis of dynamics. Here, we demonstrate improvements in the characterization of internal dynamics of methyl-bearing side chains by carbon-13 relaxometry in the small protein ubiquitin. We show that relaxometry data leads to better information about nanosecond motions as compared to high-field relaxation data only. Our calculations show that gains from relaxometry are greater with increasing correlation time of rotational diffusion.

Multiscale electrostatic embedding simulations for modeling structure and dynamics of molecules in solution: A tutorial review

AbstractThe main concepts and important technical details of electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) simulations are explained and illustrated with the intent of assisting newcomers in performing and gauging the accuracy of such simulations, focused on smaller molecules in solution. Beginners are advised on how to increase the reliability and accuracy of the simulations through benchmarking. Central considerations on methodologies for QM/MM Molecular Dynamics (MD) simulations are presented, alongside technical fundamentals regarding the construction and manipulation of simulation systems using the python‐based Atomic Simulation Environment (ASE). A worked example of QM/MM Born–Oppenheimer MD is included, and a flowchart summarizing the most salient decisions and tasks within the methodology is presented.

Combining Linear-Scaling DFT with Subsystem DFT in Born-Oppenheimer and Ehrenfest Molecular Dynamics Simulations: From Molecules to a Virus in Solution.

In this work, methods for the efficient simulation of large systems embedded in a molecular environment are presented. These methods combine linear-scaling (LS) Kohn-Sham (KS) density functional theory (DFT) with subsystem (SS) DFT. LS DFT is efficient for large subsystems, while SS DFT is linear scaling with a smaller prefactor for large sets of small molecules. The combination of SS and LS, which is an embedding approach, can result in a 10-fold speedup over a pure LS simulation for large systems in aqueous solution. In addition to a ground-state Born-Oppenheimer SS+LS implementation, a time-dependent density functional theory-based Ehrenfest molecular dynamics (EMD) using density matrix propagation is presented that allows for performing nonadiabatic dynamics. Density matrix-based EMD in the SS framework is naturally linear scaling and appears suitable to study the electronic dynamics of molecules in solution. In the LS framework, linear scaling results as long as the density matrix remains sparse during time propagation. However, we generally find a less than exponential decay of the density matrix after a sufficiently long EMD run, preventing LS EMD simulations with arbitrary accuracy. The methods are tested on various systems, including spectroscopy on dyes, the electronic structure of TiO2 nanoparticles, electronic transport in carbon nanotubes, and the satellite tobacco mosaic virus in explicit solution.

Protrusion formation during the collisional process of ethanol and water droplets: Capillary wave propagation on the water droplet

Collision processes of liquid droplets were observed to study the dynamics of molecules in solution with an apparatus which allows us to observe the collision sequence stroboscopically with time resolution of ∼1μs. The collision sequences of water–water and ethanol–water droplets were observed by production of droplets through piezo-driven nozzles. Formation of characteristic protrusion was traced in the collision of ethanol and water droplets. A model mechanism of protrusion in these systems is proposed based on the observed behavior indicating release deformation of surface tension that propagates as a capillary wave on the droplet surface.

Test of Stokes-Einstein Formula for a Tracer in a Mesoscopic Solvent by Molecular Dynamics Simulation

particles interact through multi-particle collision events which take place at discrete time intervals. Between such collision events the particles undergo free streaming motion. The dynamics conserves mass, momentum and energy and yields the exact hydrodynamic equations of motion for the conserved fields on long distance and time scales. One may consider the dynamics of solute molecules in this mesoscopic solvent and because the solvent is described at an effective particle level the solute and solvent molecules interact through intermolecular forces rather than through boundary conditions. This leads to a hybrid description of the dynamics where solute molecules evolve by Newton’s equations of motion but the solvent evolves through the multi-particle mesoscale dynamics. 2,3 Calculations of the diffusion and friction coefficients by molecular dynamics (MD) simulations are well-studied problems that have been addressed many times. Nevertheless, the computation of the friction coefficient from MD simulations involves a number of subtle issues for finite-size systems as discussed in several recent papers. 4-6 The problems center around the definition of the friction coefficient in terms of the projected dynamics and its relation to the fixed-particle friction coefficient for a massive Brownian particle. The estimates of the friction coefficients have been shown to depend on the order in which the mass of the tracer and the solvent particle number N are taken to infinity. For finite-size systems one must investigate how large N must be to obtain a reliable estimate of the friction; this typically requires very large MD simulations. Similarly, the estimate of the diffusion coefficient from the velocity autocorrelation function requires large scale simulations, especially for large tracers, due to the importance of hydrodynamic contributions. In recent papers, 7-9 the friction and diffusion coefficients of a tracer in a Lennard- Jones (LJ) solvent were evaluated by equilibrium molecular dynamics simulations in a microcanonical ensemble. The solvent molecules of diameter σ1 interact with each other through a repulsive LJ force and the tracer of diameter σ2 interacts with the solvent molecules through the same repulsive LJ force except a different LJ size or diameter parameter. These works were motivated by determination of the diffusion (D) and friction (ζ) coefficients of the tracer in the thermodynamic limit (N→∞) and by test of the Stokes-Einstein (SE) formula: D =

Karhunen–Loève Galerkin method with decimated sampling technique for the simulation of complex fluids defined in the phase space

In complex fluids, solute molecules with structural length scales much larger than atomic are dispersed in solvents of simple fluids such as water. The rheological properties of complex fluids are determined by dynamics of solute molecules which can be modeled by the Fokker–Planck equation defined in a six-dimensional phase space. In the present investigation, we devise a method of efficient simulation of complex fluid flows employing the Karhunen–Loève Galerkin (KLG) method. Adopting the decimated sampling of solvent flow fields, a reduced-order model for the Fokker–Planck equation is obtained, which can be employed for the the simulation of complex fluids with a decent computer time. As a specific example, we consider a flow of dilute polymeric liquids over a cylinder, whose constitutive equation is the FENE (finitely extensible nonlinear elastic) model. It is found that the KLG method with the decimated sampling technique yields accurate results at a computational cost less than a hundredth of that for the numerical simulation using the Fokker–Planck equation. The KLG method supplemented by the decimated sampling technique is an efficient method of coarse-graining for equations of complex fluids defined in the phase space.

Intermolecular Vibrational Motions of Solute Molecules Confined in Nonpolar Domains of Ionic Liquids

In this study, we address the following question about the dynamics of solute molecules in ionic liquids (ILs). Are the intermolecular vibrational motions of nonpolar molecules confined in the nonpolar domains formed by tail aggregation in ILs the same as those in an alkane solvent? To address this question, the optical Kerr effect (OKE) spectrum of CS(2) in the IL 1-pentyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide ([C(5)mim][NTf(2)]) was studied as a function of concentration at 295 K by the use of optical heterodyne-detected Raman-induced Kerr effect spectroscopy. The OKE spectrum broadens and shifts to higher frequency as the CS(2) concentration is decreased from 20 to 10 mol %; at lower concentrations, no further change in the width of the OKE spectrum is observed. Multicomponent line shape analysis of the OKE spectrum of 5 mol % CS(2) in [C(5)mim][NTf(2)] reveals that the CS(2) and [C(5)mim][NTf(2)] contributions to the spectrum are separable and that the CS(2) contribution is similar to the OKE spectrum of 5 mol % CS(2) in n-pentane with the spectrum being lower in frequency and narrower than that of neat CS(2). These results suggest that, at this concentration, CS(2) molecules are isolated from each other and mainly localized in the nonpolar domains of the IL.

Accounting for Triplet and Saturation Effects in FCS Measurements

Fluorescence correlation spectroscopy (FCS) is an increasingly important tool for determining low concentrations and dynamics of molecules in solution. Oftentimes triplet transitions give rise to fast blinking effects, which are accounted for by including an exponential term in the fitting of the autocorrelation function (ACF). In such cases, concomitant saturation effects also modify the amplitude and shape of the remaining parts of the ACF. We review studies of triplet and saturation effects in FCS and present a simple procedure to obtain more accurate results of particle concentrations and diffusional dynamics in experiments where triplet kinetics are evident, or where moderate laser powers approaching saturation levels are used, for example, to acquire sufficient photon numbers when observation times are limited. The procedure involves use of a modified function for curve-fitting the ACF, but there are no additional fitting parameters. Instead, a simple calibration of the total fluorescence count rate as a function of relative laser power is fit to a polynomial, and the non-linear components of this fit, together with the relative laser power used for the FCS measurement, are used to specify the magnitude of additional terms in the fitting function. Monte Carlo simulations and experiments using Alexa dyes and quantum dots, with continuous and pulsed laser excitation, demonstrate the application of the modified fitting procedure with first order correction terms, in the regime where distortions in the ACF due to photobleaching and detector dead time are small compared to those of fluorescence saturation and triplet photophysics.

13C-NMR Studies on Fluctuation of Rod-Like Molecules in Solution: Molecular Dynamics in a Polar Solvent of CDCl3

To investigate the molecular dynamics of rod-like molecules in solution, 13C-NMR measurements of a liquid crystalline material (4-(1-methylheptyloxycarbonyl)phenyl 4′-octyloxybiphenyl-4-carboxylate: MHPOBC) with a CDCl3 solvent are carried out. When MHPOBC leaves the solution and deposits as crystals, peak broadening, which may result from a slowing down of molecular motion, occurs simultaneously. In addition, the correlation time τc of the corresponding molecular motion is estimated to be approximately 10−8 s by the spin-lattice relaxation time T1 measurements.

Fluctuation Correlation Spectroscopy with a Laser-Scanning Microscope: Exploiting the Hidden Time Structure

Images obtained with a laser-scanning microscope contain a time structure that can be exploited to measure fast dynamics of molecules in solution and in cells. The spatial correlation approach provides a simple algorithm to extract this information. We describe the analysis used to process laser-scanning images of solutions and cells to obtain molecular diffusion constant in the microsecond to second timescale.

Nuclear Magnetic Resonance of Laser‐Polarized Noble Gases in Molecules, Materials, and Organisms

AbstractFor Abstract see ChemInform Abstract in Full Text.

New challenges in quantum chemistry: Quests for accurate calculations for large molecular systems.

As quantum chemistry plays a more and more central role in many complicated chemical problems, it has become necessary to obtain accurate results for large molecular systems. Conventional quantum chemistry methods are either too expensive to apply to large systems or too approximate for the results to be reliable, and they fail to satisfy this requirement. A variety of different approaches is being developed with the aim of achieving this goal: local correlation methods; divide-and-conquer methods; linear-scaling density functional methods based on the fast multipole and other approximations; effective potential methods; and hybrid methods. ONIOM (our N-layered integrated molecular orbital plus molecular mechanics method), developed by the authors, is a hybrid method in which a large molecular system is divided into onion-skin-like layers, and different quantum chemistry/molecular mechanics methods are used for different parts of the system; the results are combined to extrapolatively estimate the results of high-level calculation for the real system. Several applications of ONIOM will be discussed.

Nuclear Magnetic Resonance of Laser-Polarized Noble Gases in Molecules, Materials, and Organisms

The sensitivity of conventional nuclear magnetic resonance (NMR) techniques is fundamentally limited by the ordinarily low spin polarization achievable in even the strongest NMR magnets. However, by transferring angular momentum from laser light to electronic and nuclear spins, optical pumping methods can increase the nuclear spin polarization of noble gases by several orders of magnitude, thereby greatly enhancing their NMR sensitivity. This review describes the principles and magnetic resonance applications of laser-polarized noble gases. The enormous sensitivity enhancement afforded by optical pumping can be exploited to permit a variety of novel NMR experiments across numerous disciplines. Many such experiments are reviewed, including the void-space imaging of organisms and materials, NMR and MRI of living tissues, probing structure and dynamics of molecules in solution and on surfaces, NMR sensitivity enhancement via polarization transfer, and low-field NMR and MRI.

Formation of nanoclusters under radiation pressure in solution: A Brownian dynamics simulation study

When radiation is scattered by a medium, a part of its momentum is transferred to the target particles. This is purely a mechanical force which comes into effect when radiation is not coherently interacting. This force is known in literature as radiation pressure. Recent experimental studies have demonstrated the feasibility of using radiation pressure of a laser beam as a tool for cluster formation in solution. In this paper we describe the Brownian dynamics simulation of solute molecules under the perturbation induced by laser radiation. Here the force field generated by a laser beam in the fundamental mode is modeled as that of a two-dimensional harmonic oscillator. The radial distribution function of the perturbed system gives indication of high inhomogeneities in the solute distribution. An explicit analysis of the nature of these clusters is carried out by calculating the density–density correlation functions in the plane perpendicular to beam direction g(rxy); and along the direction of beam g(z), they give an average picture of shell structure formation in the different directions. The relaxation time of the first shell structure calculated from the van Hove correlation function is found to be relatively large in the perturbed solution. This is the signature of formation of stable nanoclusters in the presence of the radiation field. Our study on the dynamics of solute molecules during the cluster formation and dissolution gives the duration of collective relaxation, far away from the equilibrium to an equilibrium distribution. This relaxation time is found to be large for a perturbed solution.

Polarity-dependent barriers and the photoisomerization dynamics of molecules in solution

The dynamics of molecular isomerizations that involve major charge redistributions are studied using picosecond lasers. The usual assumptions that the isomerization barrier is independent of temperature and constant within a solvent series are found to be incorrect due to solvent polarity effects. Polarity and hydrogen bonding effects on isomerizations involving large dipole moment changes ( p-dimethylaminobenzonitrile) and those involving a polar intermediate ( t-stilbene) are discussed.

Solute-solvent interaction in liquids

The infrared absorption spectra of HCl and DCl in dilute CCl4 have been recorded over a range of temperatures. The band shapes have been analysed using the method of moments, allowing both the rms torque and rms force acting on the solute to be determined as functions of temperature. It is shown that rotation-translation coupling makes a significant contribution to the dynamics of these polar molecules in solution.