Molecular dynamics simulations on parallel and antiparallel C.G*G triplexes

Molecular dynamics (MD) studies have been carried out on the Hoogsteen hydrogen bonded parallel and the reverse Hoogsteen hydrogen banded antiparallel C.G*G triplexes. Earlier, the molecular mechanics studies had shown that the parallel structure was energetically more favourable than the antiparallel structure. To characterize the structural stability of the two triplexes and to investigate whether the antiparallel structure can transit to an energetically more favourable structure, due to the local fluctuations in the structure during the MD simulation, the two structures were subjected to 200ps of constant temperature vacuum MD simulations at 300K. Initially no constraints were applied to the structures and it was observed that for the antiparallel tripler, the structure showed a large root mean square deviation from the starting structure within the first 12ps and the N4-H41-O6 hydrogen bond in the WC duplex got distorted due to a high propeller twist and a moderate increase in the opening angle in the basepairs. Starting from an initial value of 30 degrees, helical twist of the average structure from this simulation had a value of 36 degrees, while the parallel structure stabilized at a twist of 33 degrees. In spite of the hydrogen bond distortions in the antiparallel tripler, it was energetically comparable to the parallel tripler. To examine the structural characteristics of an undistorted structure, another MD simulation was performed on the antiparallel tripler by constraining all the hydrogen bonds. This structure stabilized at an average twist of 33 degrees. In the course of the dynamics though the energy of the molecule - compared to the initial structure - improved, it did not become comparable to the parallel structure. Energy minimization studies performed in the presence of explicit water and counterions also showed the two structures to be equally favourable energetically Together these results indicate that the parallel C.G*G tripler with Hoogsteen hydrogen bonds also represents a stereochemically and energetically favourable structure for this class of triplexes.

Sequence Independent Recombination Triple Helices: A Molecular Dynamics Study

Recent experimental studies have shown that the Rec-A mediated homologous recombination reaction involves a triple helical intermediate, in which the third strand base forms hydrogen bonds with both the bases in the major groove of the Watson-Crick duplex. Such 'mixed' hydrogen bonds allow formation of sequence independent triplexes. DNA triple helices involving 'mixed' hydrogen bonds have been studied, using model building, molecular mechanics (MM) and molecular dynamics (MD). Models were built for a tripler comprising all four possible triplets viz., G.C*C, C.G*G, A.T*T and T.A*A. To check the stability of all the 'mixed' hydrogen bonds in such triplexes and the conformational preferences of such tripler structures, MD studies were carried out starting from two structures with 30 degrees and 36 degrees twist between the basepairs. It was observed that though the two triplexes converged towards a similar structure, the various hydrogen bonds between the WC duplex and the third strand showed differential stabilities. An MD simulation with restrained hydrogen bonds showed that the resulting structure was stable and remained close to the starting structure. These studies help us in defining stable hydrogen bond geometries involving the third strand and the WC duplex. It was observed that in the C.G*G triplets the N7 atom of the second strand is always involved in hydrogen bonding. In the G.C*C triplets, either N3 or O2 in the third strand cytosine can interchangeably act as a hydrogen bond acceptor.

Temperature-dependent chirped coherent phonon dynamics in Bi2Te3 using high-intensity femtosecond laser pulses

Degenerate pump-probe reflectivity experiments have been performed on a single crystal of bismuth telluride (Bi2Te3) as a function of sample temperature (3 K to 296 K) and pump intensity using similar to 50 femtosecond laser pulses with central photon energy of 1.57 eV. The time-resolved reflectivity data show two coherently generated totally symmetric A(1g) modes at 1.85 THz and 3.6 THz at 296 K which blue-shift to 1.9 THz and 4.02 THz, respectively, at 3 K. At high photoexcited carrier density of similar to 1.7 x 10(21) cm(-3), the phonon mode at 4.02 THz is two orders of magnitude higher positively chirped (i.e the phonon time period decreases with increasing delay time between the pump and the probe pulses) than the lower-frequency mode at 1.9 THz. The chirp parameter, beta is shown to be inversely varying with temperature. The time evolution of these modes is studied using continuous-wavelet transform of the time-resolved reflectivity data. Copyright (C) EPLA, 2010

Deformation dynamics of SS-316 Between 1023-K TO 1223-K In The Framework of Cottrell-Stokes Law

Kocks' formalism for analysing steady state deformation data for the case where Cottrell-Stokes law is valid is extended to incorporate possible back stresses from solution and/or precipitation hardening, and dependence of pre-exponential factor on the applied stress. A simple graphical procedure for exploiting these equations is demonstrated by analyzing tensile steady state data for a type 316 austentic stainless steel for the temperature range 1023 to 1223 K. In this instance, the computed back stress values turned out to be negative, a physically meaningless result. This shows that for SS 316, deformation in this temperature regime can not be interpreted in terms of a mechanism that obeys Cottrell-Stokes law.

Dielectric friction and solvation dynamics: Novel results on relaxation in dipolar liquids

In this article we present a new, general but simple, microscopic expression for time-dependent solvation energy of an ion. This expression is surprisingly similar to the expression for the time-dependent dielectric friction on a moving ion. We show that both the Chandra-Bagchi and the Fried-Mukamel formulations of solvation dynamics can be easily derived from this expression. This expression leads to an almost perfect agreement of the theory with all the available computer simulation results. Second, we show here for the first time that the mobility of a light solute ion can significantly accelerate its own solvation, specially in the underdamped limit. The latter result is also in excellent agreement with the computer simulations.

Differential stability of beta-sheets and alpha-helices in beta-lactamase: a high temperature molecular dynamics study of unfolding intermediates

Beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypical of large alpha/beta proteins with a scaffolding formed by strong noncovalent interactions. Experimentally, the enzyme is well characterized, and intermediates that are slightly less compact and having nearly the same content of secondary structure have been identified in the folding pathway. In the present study, high temperature molecular dynamics simulations have been carried out on the native enzyme in solution. Analysis of these results in terms of root mean square fluctuations in cartesian and [phi, psi] space, backbone dihedral angles and secondary structural hydrogen bonds forms the basis for an investigation of the topology of partially unfolded states of beta-lactamase. A differential stability has been observed for alpha-helices and beta-sheets upon thermal denaturation to putative unfolding intermediates. These observations contribute to an understanding of the folding/unfolding processes of beta-lactamases in particular, and other alpha/beta proteins in general.

Effect of constraints by threonine on proline containing αa-helix—A molecular dynamics approach

Proline plays an important role in the secondary structure of proteins. In the pursuit of understanding its structural role, Proline containing helices with constraints have been studied by employing molecular dynamics (MD) technique. In the present study, the constraint introduced is a threonine residue, whose sidechain has intramolecular hydrogen bond interaction with the backbone oxygen atom. The three systems that have been chosen for characterization are: (1) Ace-(Ala)12−Thr-Pro-(Ala)10−NHMe, (2) Ace-(Ala)13-Pro-Ala-Thr- (Ala)8-NHMe and (3) Ace-(Ala)13-Pro-(Ala)3-Thr-(Ala)6-NHMe. The equilibrium structures and structural transitions have been identified by monitoring the backbone dihedral angles, bend related parameters and the hydrogen bond interactions. The MD averages and root mean square (r.m.s.) fluctuations are compared and discussed. Energy minimization has been carried out on selected MD simulated points in order to analyze the characteristics of different conformations.

Molecular theory of ion solvation dynamics in water, acetonitrile and methanol: A unified microscopic description of collective dynamics in dipolar liquids

A recently developed microscopic theory of solvation dynamics in real dipolar liquids is used to calculate, for the first time, the solvation time correlation function in liquid acetonitrile, water and methanol. The calculated results are in excellent agreement with known experimental and computer simulation studies.

Optimal explicit terminal guidance for a launch vehicle

It is observed that general explicit guidance schemes exhibit numerical instability close to the injection point. This difficulty is normally attributed to the demand for exact injection which, in turn, calls for finite corrections to be enforced in a relatively short time. The deviations in vehicle state which need corrective maneuvers are caused by the off-nominal operating conditions. Hence, the onset of terminal instability depends on the type of off-nominal conditions encountered. The proposed separate terminal guidance scheme overcomes the above difficulty by minimizing a quadratic penalty on injection errors rather than demanding an exact injection. There is also a special requirement in the terminal phase for the faster guidance computations. The faster guidance computations facilitate a more frequent guidance update enabling an accurate terminal thrust cutoff. The objective of faster computations is realized in the terminal guidance scheme by employing realistic assumptions that are accurate enough for a short terminal trajectory. It is observed from simulations that one of the guidance parameters (P) related to the thrust steering angular rates can indicate the onset of terminal instability due to different off-nominal operating conditions. Therefore, the terminal guidance scheme can be dynamically invoked based on monitoring of deviations in the lone parameter P.

Proton NMR study of molecular dynamics in ammonium tribromo stannate (NH4SnBr3)

The proton second moment M2 and spin-lattice relaxation time T1 have been measured in ammonium tribromo stannate (NH4SnBr3) in the temperature range 77–300 K, to determine the ammonium dynamics. The continuous wave signal is strong and narrow at 77 and 300 K but has revealed an interesting intensity anomaly between 210 and 125 K. T1 shows a maximum (13 s) around 220 K. No minimum in the T1 vs 1000/T plot was observed down to 77 K. M2 and T1 results are interpreted in terms of NH+4 ion dynamics. The activation energy Ea for NH+4 ion reorientation is estimated to be 1.4 kcal mol−1.

Solvation dynamics in a Brownian dipolar lattice. Comparison between computer simulation and various molecular theories of solvation dynamics

Several recent theoretical and computer simulation studies have considered solvation dynamics in a Brownian dipolar lattice which provides a simple model solvent for which detailed calculations can be carried out. In this article a fully microscopic calculation of the solvation dynamics of an ion in a Brownian dipolar lattice is presented. The calculation is based on the non‐Markovian molecular hydrodynamic theory developed recently. The main assumption of the present calculation is that the two‐particle orientational correlation functions of the solid can be replaced by those of the liquid state. It is shown that such a calculation provides an excellent agreement with the computer simulation results. More importantly, the present calculations clearly demonstrate that the frequency‐dependent dielectric friction plays an important role in the long time decay of the solvation time correlation function. We also find that the present calculation provides somewhat better agreement than either the dynamic mean spherical approximation (DMSA) or the Fried–Mukamel theory which use the simulated frequency‐dependent dielectric function. It is found that the dissipative kernels used in the molecular hydrodynamic approach and in the Fried–Mukamel theory are vastly different, especially at short times. However, in spite of this disagreement, the two theories still lead to comparable results in good agreement with computer simulation, which suggests that even a semiquantitatively accurate dissipative kernel may be sufficient to obtain a reliable solvation time correlation function. A new wave vector and frequency‐dependent dissipative kernel (or memory function) is proposed which correctly goes over to the appropriate expressions in both the single particle and the collective limits. This form is expected to lead to better results than all the existing descriptions.

Solvation dynamics in liquid water. A novel interplay between librational and diffusive modes

A microscopic calculation of the solvation dynamics of an ion in liquid water is presented. The calculated solvation time correlation function shows an ultrafast Gaussian decay which carries about 70%–90% of the strength followed by a biexponential decay with time constants equal to 250 fs and 1 ps. These results are in excellent agreement with the computer simulations of Maroncelli and Fleming and also with the experimental findings of Barbara and Jarzeba. In addition, we find that both the rotational librations and the intermolecular translational vibrational modes of water contribute significantly to the initial Gaussian decay.

Sorbate properties and cage-to-cage diffusion of argon in NaCaA: a molecular dynamics study

Detailed molecular dynamics simulations of argon in zeolite NaCaA are reported. Thermodynamic, structural, and dynamical properties of the sorbate as a function of temperature have been obtained. The properties calculated include various site-site radial distribution functions, different energy distribution functions, selfdiffusion coefficients, the power spectra, and properties relating to cage-to-cage diffusion. The results suggest that sorbate is delocalized above 300 K. Both modes of cage-to-cage diffusion-the surface-mediated and centralized diffusion-are associated with negative barrier heights. Surprisingly, rate of cage-to-cage diffusion is associated with negative and positive activation energies below and above 500 K. The observed differences in the behavior of the rate of cage-to-cage diffusion between Xe-NaY and Ar-NaCaA systems and the nature of the potential energy surface are discussed. Presence of sorbatezeolite interactions results in significant enhancement in the rate of cage-to-cage diffusion and rate of cage visits. It is shown that properties dependent on the long-time behavior such as the diffusion coefficient and the rate of cages visited exhibit the expected Arrhenius dependence on temperature.

DNA Compaction by a Dendrimer

At physiological pH, a PAMAM dendrimer is positively charged and can effectively bind negatively charged DNA. Currently, there has been great interest in understanding this complexation reaction both for fundamental (as a model for complex biological reactions) as well as for practical (as a gene delivery material and probe for sensing DNA sequence) reasons. Here, we have studied the complexation between double-stranded DNA (dsDNA) and various generations of PAMAM dendrimers (G3-05) through atomistic molecular dynamics simulations in the presence of water and ions. We report the compaction of DNA on a nanosecond time scale. This is remarkable, given the fact that such a short DNA duplex with a length close to 13 nm is otherwise thought to be a rigid rod. Using several nanoseconds long MD simulations, we have observed various binding modes of dsDNA and dendrimers for various generations of PAMAM dendrimers at varying charge ratios, and it confirms some of the binding modes proposed earlier. The binding is driven by the electrostatic interaction, and the larger the dendrimer charge, the stronger the binding affinity. As DNA wraps/binds to the dendrimer, counterions originally condensed onto DNA (Na+) and the dendrimer (Cl-) get released. We calculate the entropy of counterions and show that there is gain in entropy due to counterion release during the complexation. MD simulations demonstrate that, when the charge ratio is greater than 1 (as in the case of the G5 dendrimer), the optimal wrapping of DNA is observed. Calculated binding energies of the complexation follow the trend G5 > 04 > 03, in accordance with the experimental data. For a lower-generation dendrimer, such as G3, and, to some extent, for G4 also, we see considerable deformation in the dendrimer structure due to their flexible nature. We have also calculated the various helicoidal parameters of DNA to study the effect of dendrimer binding on the structure of DNA. The B form of the DNA is well preserved in the complex, as is evident from various helical parameters, justifying the use of the PAMAM dendrimer as a suitable delivery vehicle.