Biological water: Femtosecond dynamics of macromolecular hydration

The unique features of a macromolecule and water as a solvent make the issue of solvation unconventional, with questions about the static versus dynamic nature of hydration and the, physics of orientational and translational diffusion at the boundary. For proteins, the hydration shell that covers the surface is critical to the stability of its structure and function. Dynamically speaking, the residence time of water at the surface is a signature of its mobility and binding. With femtosecond time resolution it is possible to unravel the shortest residence times which are key for the description of the hydration layer, static or dynamic. In this article we review these issues guided by experimental studies, from this laboratory, of polar hydration dynamics at the surfaces of two proteins (Subtilisin Carlsberg (SC) and Monellin). The natural probe tryptophan amino acid was used for the interrogation of the dynamics, and for direct comparison we also studied the behavior in bulk water - a complete hydration in 1 ps. We develop a theoretical description of solvation and relate the theory to the experimental observations. In this - theoretical approach, we consider the dynamical equilibrium in the hydration shell, defining the rate processes for breaking and making the transient hydrogen bonds, and the effective friction in the layer which is defined by the translational and orientational motions of water molecules. The relationship between the residence time of water molecules and the observed slow component in solvation dynamics is a direct one. For the two proteins studied, we observed a "bimodal decay" for the hydration correlation function, with two primary relaxation times: ultrafast, typically 1 ps or less, and longer, typically 15-40 ps, and both are related to the residence time at the protein surface, depending on the binding energies. We end by making extensions to studies of the denatured state of the protein, random coils, and the biomimetic micelles, and conclude with our thoughts on the relevance of the dynamics of native structures to their functions.

Comparison of the ultrafast to slow time scale dynamics of three liquid crystals in the isotropic phase

The dynamics of three liquid crystals, 4'(pentyloxy)-4-biphenylcarbonitrile (5-OCB), 4'-pentyl-4-biphenylcarbonitrile (5-CB), and 1-isothiocyanato-(4-propylcyclohexyl)benzene (3-CHBT), are investigated from very short time (similar to1 ps) to very long time (>100 ns) as a function of temperature using optical heterodyne detected optical Kerr effect experiments. For all three liquid crystals, the data decay exponentially only on the longest time scale (> several ns). The temperature dependence of the long time scale exponential decays is described well by the Landau-de Gennes theory of the randomization of pseudonematic domains that exist in the isotropic phase of liquid crystals near the isotropic to nematic phase transition. At short time, all three liquid crystals display power law decays. Over the full range of times, the data for all three liquid crystals are fit with a model function that contains a short time power law. The power law exponents for the three liquid crystals range between 0.63 and 0.76, and the power law exponents are temperature independent over a wide range of temperatures. Integration of the fitting function gives the empirical polarizability-polarizability (orientational) correlation function. A preliminary theoretical treatment of collective motions yields a correlation function that indicates that the data can decay as a power law at short times. The power law component of the decay reflects intradomain dynamics. (C) 2002 American Institute of Physics.

Dynamics of crystal size distributions with size-dependent rates

The growth and dissolution dynamics of nonequilibrium crystal size distributions (CSDs) can be determined by solving the governing population balance equations (PBEs) representing reversible addition or dissociation. New PBEs are considered that intrinsically incorporate growth dispersion and yield complete CSDs. We present two approaches to solving the PBEs, a moment method and a numerical scheme. The results of the numerical scheme agree with the moment technique, which can be solved exactly when powers on mass-dependent growth and dissolution rate coefficients are either zero or one. The numerical scheme is more general and can be applied when the powers of the rate coefficients are non-integers or greater than unity. The influence of the size dependent rates on the time variation of the CSDs indicates that as equilibrium is approached, the CSDs become narrow when the exponent on the growth rate is less than the exponent on the dissolution rate. If the exponent on the growth rate is greater than the exponent on the dissolution rate, then the polydispersity continues to broaden. The computation method applies for crystals large enough that interfacial stability issues, such as ripening, can be neglected. (C) 2002 Elsevier Science B.V. All rights reserved.

Excited state structure and dynamics of p-benzoquinone and bromanil from time-resolved resonance Raman spectra and simulation

p-Benzoquinone and its halogen substituted derivatives are known to have differing reactivities in the triplet excited state. While bromanil catalyzes the reduction of octaethylporphyrin most efficiently among the halogenated p-benzoquinones, the reaction does not take place in presence of the unsubstituted p-benzoquinone (T. Nakano and Y. Mori, Bull. Chem. Soc. Jpn., 67, 2627 (1994)). Understanding of such differences requires a detailed knowledge of the triplet state structures, normal mode compositions and excited state dynamics. In this paper, we apply a recently presented scheme (M. Puranik, S. Umapathy, J. G. Snijders, and J. Chandrasekhar, J. Chem, Phys., 115, 6106 (2001)) that combines parameters from experiment and computation in a wave packet dynamics simulation to the triplet states of p-benzoquinone and bromanil. The absorption and resonance Raman spectra of both the molecules have been simulated. The normal mode compositions and mode specific excited state displacements have been presented and compared. Time-dependent evolution of the absorption and Raman overlaps for all the observed modes has been discussed in detail. In p-benzoquinone, the initial dynamics is along the C=C stretching and C-H bending modes whereas in bromanil nearly equal displacements are observed along all the stretching coordinates.

Nonlinear dynamics of eucaryotic pyruvate dehydrogenase multienzyme complex: Decarboxylation rate, oscillations, and multiplicity

Pyruvate conversion to acetyl-CoA by the pyruvate dehydrogenase (PDH) multienzyme complex is known as a key node in affecting the metabolic fluxes of animal cell culture. However, its possible role in causing possible nonlinear dynamic behavior such as oscillations and multiplicity of animal cells has received little attention. In this work, the kinetic and dynamic behavior of PDH of eucaryotic cells has been analyzed by using both in vitro and simplified in vivo models. With the in vitro model the overall reaction rate (v(1)) of PDH is shown to be a nonlinear function of pyruvate concentration, leading to oscillations under certain conditions. All enzyme components affect v, and the nonlinearity of PDH significantly, the protein X and the core enzyme dihydrolipoamide acyltransferase (E2) being mostly predominant. By considering the synthesis rates of pyruvate and PDH components the in vitro model is expanded to emulate in vivo conditions. Analysis using the in vivo model reveals another interesting kinetic feature of the PDH system, namely, multiple steady states. Depending on the pyruvate and enzyme levels or the operation mode, either a steady state with high pyruvate decarboxylation rate or a steady state with significantly lower decarboxylation rate can be achieved under otherwise identical conditions. In general, the more efficient steady state is associated with a lower pyruvate concentration. A possible time delay in the substrate supply and enzyme synthesis can also affect the steady state to be achieved and lead's to oscillations under certain conditions. Overall, the predictions of multiplicity for the PDH system agree qualitatively well with recent experimental observations in animal cell cultures. The model analysis gives some hints for improving pyruavte metabolism in animal cell culture.

Photodissociation dynamics of CH2ICl at 222, 236, 266, 280, and-304 nm

Dynamics of I*(P-2(1/2)) formation from CH2ICl dissociation has-been investigated at five different ultraviolet excitation wavelengths, e.g., 222, 236, 266, 280, and similar to304 nm. The quantum yield of I*((2)p(1/2)) production, phi*, has been measured by monitoring nascent I(P-2(3/2)) and I* concentrations using a resonance enhanced multiphoton ionization detection scheme. The measured quantum yield as a function of excitation energy follows the same trend as that of methyl iodide except at 236 run. The photodissociation dynamics of CH2ICl also involves three upper states similar to methyl iodide, and a qualitative correlation diagram has been constructed to account for the observed quantum yield. From the difference in behavior at 236 nm, it appears that the crossing region between the two excited states ((3)Q(0) and (1)Q(1)) is located near the exit valley away from the Franck Condon excitation region. The B- and C-band transitions do not participate in the dynamics, and the perturbation of the methyl iodide states due to Cl-I interaction is relatively weak at the photolysis wavelengths employed in this investigation.

Slow orientational dynamics of water molecules at a micellar surface

The dynamics of water molecules near an aqueous micellar interface is studied in an atomistic molecular dynamics simulation of cesium pentadecafluorooctanoate (CsPFO) in water. The dipolar orientational time correlation function (tcf) and the translational diffusion of the water molecules are investigated. Results show that both the reorientational and the translational motion of water molecules near the micelle are restricted. In particular, the orientational tcf exhibits a very slow component in the long time which is slower than its bulk value by 2 orders of magnitude. This slow decay seems to be related to the slow decay often observed in experiments. The origin of the slow decay is analyzed.

Effect of orientational motion of mobile chromophores on the dynamics of Forster energy transfer in polymers

Brownian dynamics (BD) simulations have been carried out to explore the effects of the orientational motion of the donor-acceptor (D-A) chromophore pair on the Forster energy transfer between the D-A pair embedded in a polymer chain in solution. It is found that the usually employed orientational averaging (that is, replacing the orientational factor, kappa, by kappa (2) = 2/3) may lead to an error in the estimation of the rate of the reaction by about 20%. In the limit of slow orientational relaxation, the preaveraging of the orientational factor leads to an overestimation of the rate, while in the opposite limit of very fast orientational relaxation, the usual scheme underestimates the rate. The latter results from an interesting interplay between reaction and diffusion. On the other hand, when one of the chromophores is fixed, the preaveraged rate is found to be fairly reliable if the rotational relaxation of the chromophore is sufficiently fast. The present study also reveals a power law dependence of the FRET rate on the chain length (rate proportional to N- alpha, with alpha approximate to 2.6).

Nonlinear Dynamics of Beams with Stochastic Parameter Variations

The aim of this paper is to investigate the steady state response of beams under the action of random support motions. The study is of relevance in the context of earthquake response of extended land based structures such as pipelines and long span bridges, and, secondary systems such as piping networks in nuclear power plant installations. The following complicating features are accounted for in the response analysis: (a) differential support motions: this is characterized in terms of cross power spectral density functions associated with distinct support motions, (b) nonlinear support conditions, and (c) stochastically inhomogeneous stiffness and mass variations of the beam structure; questions on non-Gaussian models for these variations are considered. The method of stochastic finite elements is combined with equivalent linearization technique and Monte Carlo simulations to obtain response moments.

Synthesis, structural characterization, thermal studies and chain dynamics of poly(methacrylonitrile peroxide) by NMR spectroscopy

Poly(methacrylonitrile peroxide) (PMNP) has been synthesized from methacrylonitrile by free radical initiated oxidative polymerization and characterized by different spectroscopic methods. NMR spectroscopy confirmed the alternating copolymer structure with labile peroxy bonds in the main chain. The extreme instability of PMNP was noted from FTIR spectroscopy. Thermal degradation studies by using differential scanning calorimetry and thermogravimetry have revealed that PMNP degrades highly exothermically and the heat of degradation, 42.5 kcal mol−1, is of the same order as that reported for other vinyl polyperoxides. Mass spectral fragmentation pattern under electron impact (EI) condition has also been investigated. The mechanism of the primary exothermic degradation has been substantiated by thermochemical calculations. The chain dynamics of the polyperoxide chain has been studied by means of 13C spin–lattice relaxation times (T1) of the main chain as well as the side chain carbons. The temperature dependence of the spin–lattice relaxation times shows that the PMNP is more flexible compared to the analogous poly(styrene peroxide).

On the dynamics of activation of mammalian X chromosomes

We have investigated a mathematical model of the process of activation of the X chromosomes in eutherian mammals. The model assumes that the activation is brought about over some definite time interval T by the complete saturation of N receptor sites on an X chromosome by M activating molecules (or multiples of M). The probability λ of a first hit on the receptor site is considered to be very much lower than that of subsequent hits; that is, we assume strong co-operative binding. Assuming further that an incomplete saturation of receptor sites is malfunctional, we can show that for proper activation of X chromosomes in normal diploid males and females, we must have λMT ≥ 3 and 0·96 ≤ N/M ≤ 1. An extension of this analysis for the triploid cases shows that under these conditions, we cannot explain the activation of two X's if the number of activating molecules is fixed at M. This suggests that there must be two classes of triploid embryos differing from each other in a step-wise manner in the number of activating molecules. In other words, triploids with two active X chromosomes would require 2M activating molecules as opposed to M molecules in triploids with a single active X. This interpretation of the two classes of triploids would be consistent with differing imprinting histories of the parental contributions to the triploid zygote.

The collective dynamics of self-propelled particles

We propose a method for the dynamic simulation of a collection of self-propelled particles in a viscous Newtonian fluid. We restrict attention to particles whose size and velocity are small enough that the fluid motion is in the creeping flow regime. We propose a simple model for a self-propelled particle, and extended the Stokesian Dynamics method to conduct dynamic simulations of a collection of such particles. In our description, each particle is treated as a sphere with an orientation vector p, whose locomotion is driven by the action of a force dipole Sp of constant magnitude S0 at a point slightly displaced from its centre. To simplify the calculation, we place the dipole at the centre of the particle, and introduce a virtual propulsion force Fp to effect propulsion. The magnitude F0 of this force is proportional to S0. The directions of Sp and Fp are determined by p. In isolation, a self-propelled particle moves at a constant velocity u0 p, with the speed u0 determined by S0. When it coexists with many such particles, its hydrodynamic interaction with the other particles alters its velocity and, more importantly, its orientation. As a result, the motion of the particle is chaotic. Our simulations are not restricted to low particle concentration, as we implement the full hydrodynamic interactions between the particles, but we restrict the motion of particles to two dimensions to reduce computation. We have studied the statistical properties of a suspension of self-propelled particles for a range of the particle concentration, quantified by the area fraction φa. We find several interesting features in the microstructure and statistics. We find that particles tend to swim in clusters wherein they are in close proximity. Consequently, incorporating the finite size of the particles and the near-field hydrodynamic interactions is of the essence. There is a continuous process of breakage and formation of the clusters. We find that the distributions of particle velocity at low and high φa are qualitatively different; it is close to the normal distribution at high φa, in agreement with experimental measurements. The motion of the particles is diffusive at long time, and the self-diffusivity decreases with increasing φa. The pair correlation function shows a large anisotropic build-up near contact, which decays rapidly with separation. There is also an anisotropic orientation correlation near contact, which decays more slowly with separation. Movies are available with the online version of the paper.

Dynamics of bound dyes in a nonpolymeric aqueous gel derived from a tripodal bile salt

Rotational dynamics of polarity sensitive fluorescent dyes (ANS and DPH) in a nonpolymertic aqueous gel derived from tripodal cholamide I was studied using ultrafast time-resolved fluorescence technique. Results were compared with that of naturally occurring di- and trihydroxy bile salts. ANS in the gel showed two rotational correlation time (phi) components, 13.2 ns (bound to the hydrophobic region of the gel) and 1.0 ns (free aqueous ANS), whereas DPH showed only one component (4.8 ns). In the sol state, faster rotational motion was observed, both for ANS and DPH. Our data revealed that dyes get encapsulated more tightly in the gel network when compared to the micellar aggregates. ANS has more restrained rotation compared to DPH. This was attributed to the interaction of the sulfonate group of ANS with water molecules and hydrophilic parts of the gelator molecule. No restricted rotation was observed for DPH in the gel state unlike when it is in the gel phase of lipid bilayer.

Dynamics of pulsed flow in an elastic tube

Internal haemorrhage, often leading to cardio-vascular arrest happens to be one of the prime sources of high fatality rates in mammals. We propose a simplistic model of fluid flow in our attempt to specify the location of the haemorrhagic spot, which, if located accurately, could possibly be operated leading to an instant cure. The model we employ for the purpose is basically fluid mechanical in origin and consists of a viscous fluid, pumped by a periodic force and flowing through an elastic tube. The analogy is with that of blood, pumped from the heart and flowing through an artery or vein. Our results, aided by graphical illustrations, match reasonably well with experimental observations.

Dynamics of water at the interface of a small protein, enterotoxin

Fully atomistic molecular dynamics simulations have been carried out to investigate the correlation of biological activity with dynamics of water molecules in an aqueous protein solution of the toxic domain of enterotoxin (PDB ID: 1ETN). This is a small protein of 13 amino acid residues. Our study of this water soluble protein clearly reveals that water dynamics slows down in the hydration layer. Despite this general slowing down, water molecules in the vicinity of the second beta turn of this protein exhibit faster dynamics than those near other regions of the protein. Since this beta turn is believed to play a critical role in the receptor binding of this protein, the faster dynamics of water near the beta turn m ay have biological significance. The collective orientational dynamics of the water molecules in the protein solution exhibits a characteristic long time component of 27 ps, which agrees well with dielectric relaxation experiments.