MPSA effects on copper electrodeposition investigated by molecular dynamics simulations

In superconformal filling of copper-chip interconnects, organic additives are used to fill high-aspect-ratio trenches or vias from the bottom up. In this study we report on the development of intermolecular potentials and use molecular dynamics simulations to provide insight into the molecular function of an organic additive (3-mercaptopropanesulfonic acid or MPSA) important in superconformal electrodeposition. We also investigate how the presence of sodium chloride affects the surface adsorption and surface action of MPSA as well as the charge distribution in the system. We find that NaCl addition decreases the adsorption strength of MPSA at a simulated copper surface and attenuates the copper-ion association with MPSA. The model also was used to simulate induced-charge effects and adsorption on a nonplanar electrode surface.     

Kinetics of NaCl nucleation in supercritical water investigated by molecular dynamics simulations

At system pressures between 17 MPa and 25 MPa the nucleation and growth of NaCl nanoparticles in water at supercritical conditions was investigated by molecular dynamics simulations at different system temperatures and system densities. Our results show that particle formation takes place within a few hundred picoseconds after the jump from ambient to supercritical conditions. After nucleation a phase of growth by adding monomers is followed by growth via cluster-cluster collisions. We present results on the time development of distributions of cluster sizes, cluster compositions, and cluster temperatures as well as radial distribution functions and nucleation rates.     

Aggregation of FeCl2 clusters in supercritical water investigated by molecular dynamics simulations

We have carried out molecular dynamics (MD) simulations of the aggregation of FeCl 2 clusters in supercritical water. The particle formation in systems of 2048 water molecules (rigid SPC/E-model) and 120 Fe (2+) ions and 240 Cl (-) ions has been investigated for 250 ps at five different state points at temperatures from 798 to 873 K and system densities from 0.18 g/cm (3) to 0.13 g/cm (3). We describe the particle growth by means of properties of the largest cluster in a system as well as cluster size averaged and time averaged observables. From preexisting or immediately formed units of Fe (2+)-Cl (-), Fe (2+)-Cl (-) 2, Fe (2+)-Cl (-) 3 etc., the further growth of clusters is dominated by aggregation of such small building blocks. Clusters up to 10 ions in size with large charge imbalances are found during the growth process while a balanced positive to negative charge ratio is found on the average with time and cluster size development. Water molecules are found within the FeCl 2 clusters during the whole time interval covered by the simulations, which is in agreement with the existence of crystal water in FeCl 2 crystals grown from aqueous solutions. The radial distribution functions obtained from the simulation data are in good agreement with experimental results of slightly distorted FeCl 2.4H 2O crystals.     

Structure of liquid formic acid investigated by first principle and classical molecular dynamics simulations

The structure of liquid formic acid has been investigated by Car-Parrinello and classical molecular dynamics simulations, focusing on the characterization of the H-bond network and on the mutual arrangement of pairs of bonded molecules. In agreement with previous computational studies, two levels of H-bonded structures have been found. Small clusters, characterized by O-H...O bonds, are held together by weak C-H...O bonds to form large branched structures. From the ab initio simulation we infer the importance of cyclic H-bond dimer configurations, typical of the gas phase. Most of these dimer structures are however found to be embedded into H-bonded chains. When only O-H...O bonds are taken into account, linear H-bond chains are detected as basic structures of the liquid. More branched structures occur when C-H...O bonds are also considered. Regarding the arrangement of molecular pairs, we observed that O-H...O bonds favor the occurrence of configurations with parallel molecular planes, whereas no preferential orientation is observed for molecules forming C-H...O bonds.     

Backbone dynamics of proteins studied by two-dimensional heteronuclear NMR spectroscopy and molecular dynamics simulations

To investigate the backbone dynamics of proteins ¹⁵N longitudinal and transverse relaxation experiments combined with {¹H, ¹⁵N{ NOE measurements together with molecular dynamics simulations were carried out using ribonuclease T₁ and the complex of ribonuclease T₁ with 2′GMP as a model protein. The intensity decay of individual amide cross peaks in a series of (¹H, ¹⁵N)HSQC spectra with appropriate relaxation periods was fitted to a single exponential by using a simplex algorithm in order to obtain ¹⁵N T₁ and T₂ relaxation times. The relaxation times were analyzed in terms of the “model-free” approach introduced by Lipari and Szabo. In addition, a nanosecond molecular dynamics (MD ) simulation of ribonuclease T₁ and its 2′GMP complex in water was carried out. The angular reorientations of the backbone amide groups were classified with several coordinate frames following a transformation of NH vector trajectories. In this study, NH librations and backbone dihedral angle fluctuations were distinguished. The NH bond librations were found to be similar for all amides as characterized by correlation times of librational motions in a subpicosecond scale. The angular amplitudes of these motions were found to be about 10°–12° for out-of-plane displacements and 3°–5° for the in-plane displacement. The contributions from the much slower backbone dihedral angle fluctuations strongly depend on the secondary structure. The dependence of the amplitude of local motion on the residue location in the backbone is in good agreement with the results of NMR relaxation measurements and the X-ray data. The protein dynamics is characterized by a highly restricted local motion of those parts of the backbone with defined secondary structure as well as by a high flexibility in loop regions. Comparison of the MD and NMR data of the free liganded enzyme ribonuclease T₁ clearly indicates a restriction of the mobility within certain regions of the backbone upon inhibitor binding. © 1996 John Wiley & Sons, Inc.     

The Mg2+ binding sites of the 5S rRNA loop E motif as investigated by molecular dynamics simulations

Molecular dynamics simulations have been used to investigate the binding of Mg(2+) ions to the deep groove of the eubacterial 5S rRNA loop E. The simulations suggest that long-lived and specific water-mediated interactions established between the hydrated ions and the RNA atoms lining up the binding sites contribute to the stabilization of this motif. The Mg(2+) binding specificity is modulated by two factors: (i) a required electrostatic complementarity and (ii) a structural correspondence between the hydrated ion and its binding pocket that can be estimated by its degree of dehydration and the resulting number and lifetime of the intervening water-mediated contacts. Two distinct binding modes for pentahydrated Mg(2+) ions that result in a significant freezing of the tumbling motions of the ions are described, and mechanistic details related to the stabilization of nucleic acids by divalent ions are provided.     

Confinement and surface effects on the molecular dynamics of a nematic mixture investigated by dielectric relaxation spectroscopy

Broadband dielectric spectroscopy (10(-2)-10(9) Hz) was employed to investigate the molecular dynamics of the liquid crystalline mixture E7 confined in both untreated and lecithin-treated 20 nm Anopore membranes. Because E7 does not crystallize, it was possible to cover a temperature range of more than 200 K, providing an exhaustive dielectric characterization of a liquid crystal confined to Anopore membranes for the first time. In the nematic state, the tumbling (alpha-) and the delta-relaxation are observed, also under confinement conditions. The analysis of their relative intensities give that the orientation of the E7 molecules is preferentially axial in untreated but opposite radial in lecithin-treated pores. The radial alignment of the liquid crystals in the modified membrane is understood as a tail-to-tail conformation of E7 molecules imposed by the adsorbed lecithin molecules. The relaxation rate of the alpha-process is enhanced for E7 confined in native Anopore compared with the bulk and E7 in treated pores. This is interpreted as resulting from a less dense molecular packing of E7 in the middle of the pore compared to the bulk. In both untreated and treated membranes, the relaxation rate of the delta-process is higher than in the bulk, and the values of the respective Vogel-Fulcher-Tammann temperatures depend on the actual surface treatment. Additionally, a surface process, due to molecular fluctuations of molecules within an adsorbed layer at the pore wall, was detected.     

The NMR structure of [Xd(C2)]4 investigated by molecular dynamics simulations

The i‐motif tetrameric structure is built up from two parallel duplexes intercalated in a head‐to‐tail orientation, and held together by hemiprotonated cytosine pairs. Two topologies exist for the i‐motif structure, one with outermost 3′ extremities and the other with outermost 5′ extremities, called the 3′E and 5′E topology, respectively. Since the comparison of sugar and phosphate group interactions between the two topologies is independent of the length of the intercalation motif, the relative stability of the 3′E and 5′E topologies therefore should not depend on this length. Nevertheless, it has been shown that the 3′E topology of the [d(C2)]4 is much more stable than the 5′E topology, and that the former is the only species observed in solution. In order to understand the reason for this atypical behavior, the NMR structure of the [Xd(C2)]4 was determined and analyzed by molecular dynamics simulations. In the NMR structure, the width of the narrow groove is slightly smaller than in previously determined i‐motif structures, which supports the importance of phosphodiester backbone interactions in the structure stability. The simulations show that the stacking of cytosines, essential for the i‐motif stability, is produced by a similar and non‐negative twisting of the phosphodiester backbones. The twisting is induced by an interaction between the backbones; the [Xd(C2)]4 in 5′E topology, exhibiting very limited interaction between the phosphodiester backbones, is thus unstable. Copyright © 2002 John Wiley & Sons, Ltd.     

Conformational analysis of a tetrasaccharide based on NMR spectroscopy and molecular dynamics simulations

The conformational preference of the human milk oligosaccharide lacto-N-neotetraose, beta-d-Galp-(1 --> 4)-beta-d-GlcpNAc-(1 --> 3)-beta-d-Galp-(1 --> 4)-d-Glcp, has been analyzed using (1)H,(1)H T-ROESY and (1)H,(13)C trans-glycosidic J coupling experiments in isotropic solution and (1)H,(13)C residual dipolar couplings (RDCs) obtained in lyotropic liquid crystalline media. Molecular dynamics simulations of the tetrasaccharide with explicit water as the solvent revealed that two conformational states are significantly populated at the psi glycosidic torsion angle, defined by C(anomeric)-O-C-H, of the (1 --> 3)-linkage. Calculation of order parameters, related to the molecular shape, were based on the inertia tensor and fitting of experimental RDCs to different conformational states showed that psi(+) > 0 degrees is the major and psi(-) < 0 degrees is the minor conformation in solution, in complete agreement with a two-state analysis based on the T-ROESY data. Attention was also given to the effect of salt (200 mM NaCl) in the anisotropic medium, which was a ternary mixture of n-octyl-penta(ethylene glycol), n-octanol, and D(2)O.     

Effect of acetone accumulation on structure and dynamics of lipid membranes studied by molecular dynamics simulations

The modulation of the properties and function of cell membranes by small volatile substances is important for many biomedical applications. Despite available experimental results, molecular mechanisms of action of inhalants and organic solvents, such as acetone, on lipid membranes remain not well understood. To gain a better understanding of how acetone interacts with membranes, we have performed a series of molecular dynamics (MD) simulations of a POPC bilayer in aqueous solution in the presence of acetone, whose concentration was varied from 2.8 to 11.2 mol%. The MD simulations of passive distribution of acetone between a bulk water phase and a lipid bilayer show that acetone favors partitioning into the water-free region of the bilayer, located near the carbonyl groups of the phospholipids and at the beginning of the hydrocarbon core of the lipid membrane. Using MD umbrella sampling, we found that the permeability barrier of ∼0.5 kcal/mol exists for acetone partitioning into the membrane. In addition, a Gibbs free energy profile of the acetone penetration across a bilayer demonstrates a favorable potential energy well of −3.6 kcal/mol, located at 15–16 Å from the bilayer center. The analysis of the structural and dynamics properties of the model membrane revealed that the POPC bilayer can tolerate the presence of acetone in the concentration range of 2.8–5.6 mol%. The accumulation of the higher acetone concentration of 11.2 mol% results, however, in drastic disordering of phospholipid packing and the increase in the membrane fluidity. The acetone molecules push the lipid heads apart and, hence, act as spacers in the headgroup region. This effect leads to the increase in the average headgroup area per molecule. In addition, the acyl tail region of the membrane also becomes less dense. We suggest, therefore, that the molecular mechanism of acetone action on the phospholipid bilayer has many common features with the effects of short chain alcohols, DMSO, and chloroform.     

Effect of bromide on the interfacial structure of aqueous tetrabutylammonium iodide: Photoelectron spectroscopy and molecular dynamics simulations

Solvation of surface-active tetrabutylammonium iodide (TBAI) in liquid water and in sodium bromide aqueous solution was investigated by VUV photoelectron spectroscopy and by molecular dynamics simulations. The observed signal intensity changes in the photoemission spectra are consistent with the varying propensities of the different ions for the solution interface. While the cations are surface-bound due to hydrophobic interactions, the anions are driven to the vacuum/solution interface by their large polarizability and size. Iodide is more polarizable, and hence more surface-active than bromide, which explains the relatively small decrease of the iodide photoemission signal when TBAI is dissolved in bromide solution.     

Structural basis of specific binding between Aurora A and TPX2 by molecular dynamics simulations

In the present study, the impacts of G198N and W128F mutations on the recognition between Aurora A and targeting protein of Xenopus kinesin-like protein 2 (TPX2) were investigated using molecular dynamics (MD) simulations, free energy calculations, and free energy decomposition analysis. The predicted binding free energy of the wild-type complex is more favorable than those of three mutants, indicating that both single and double mutations are unfavorable for the Aurora A and TPX2 binding. It is also observed that the mutations alternate the binding pattern between Aurora A and TPX2, especially the downstream of TPX2. An intramolecular hydrogen bond between the atom OD of Asp11(TPX2) and the atom HE1 of Trp34(TPX2) disappear in three mutants and thus lead to the instability of the secondary structure of TPX2. The combination of different molecular modeling techniques is an efficient way to understand how mutation has impacts on the protein-protein binding and our work gives valuable information for the future design of specific peptide inhibitors for Aurora A.     

Free volume from molecular dynamics simulations and its relationships to the positron annihilation lifetime spectroscopy

The free volume micro-structural properties of propylene glycol obtained by means of molecular dynamics simulations have been investigated and compared with the experimental data from positron annihilation lifetime spectroscopy (PALS). The results are also compared to those recently obtained on glycerol. The bulk microstructures of the samples have been analyzed in the temperature range 100–350 K with a probe-based procedure for exploring the free volume cavities of the microstructures. The basic free volume property, i.e., mean cavity volume, is compared with the hole volume data from PALS. A comparison between calculated and experimental data suggests the existence of a threshold volume for the smallest cavity detectable by PALS, which may be ascribed to fast local motions of the matrix constituents. At high temperatures the cavity analysis reveals the formation of an infinite cavity, i.e., percolation phenomenon. The onset temperatures of the percolation process in propylene glycol and glycerol are found to be close to the characteristic PALS temperature \(T^{\rm L}_{\rm b2}\) , where a pronounced change in the PALS response occurs, as well as to the characteristic dynamic Schönhals temperature \(T^{\rm SCH}_{\rm B}\) , and Stickel’s temperature \(T^{\rm ST}_{\rm B}\) , marking a dramatic change in the primary α properties.     

Formation of FeCl(2)/NaCl-nanoparticles in supercritical water investigated by molecular dynamics simulations: nucleation rates

Nucleation and growth of FeCl(2) in supercritical water containing NaCl at different state points between temperatures of 798 and 873 K and system densities between 0.24 and 0.14 g cm(-3) have been studied by molecular dynamics simulations. The number of NaCl ion pairs was chosen to simulate particle formation in seawater and brine of higher salinity. Rigid SPC/E water was used to model the water molecules while a combination of Coulomb and Lennard-Jones potentials was used for the ions. Two different methods for determination of nucleation rates are applied and their results compared. We find decreasing nucleation rates with both increasing temperature and decreasing system density. Our results are also compared to those we recently obtained in an investigation of pure FeCl(2) from supercritical water. We find both increasing nucleation rates and a decreasing size of the critical cluster with increasing amount of NaCl.     

In vitro study on the binding of herbicide glyphosate to human serum albumin by optical spectroscopy and molecular modeling

In this study, the interaction mechanism of herbicide glyphosate and human serum albumin (HSA) has been characterized by fluorescence, UV, Fourier transform infrared (FT-IR), Circular dichroism (CD) spectroscopic and molecular modeling methods. The structural characteristics of glyphosate and HSA were probed, and affinity constants were determined under different temperatures. The enthalpy change (DeltaH degrees ) and the entropy changes (DeltaS degrees ) were calculated to be -21.78kJmol(-1) and 6.38Jmol(-1)K(-1) according to the Van't Hoff equation. These results indicated that glyphosate binds to HSA mainly by hydrogen bond and hydrophobic interaction can also not be excluded, which is in good agreement with the results from modeling experiment. The average binding distance, r, between the donor (HSA) and the acceptor (glyphosate) was evaluated and found to be 2.89nm according to the F?rster's theory of non-radiation energy transfer. The alterations of protein secondary structure in the presence of glyphosate were confirmed by the evidences from UV, FT-IR and CD spectroscopes.     

Recognition of RNA by amide modified backbone nucleic acids: molecular dynamics simulations of DNA-RNA hybrids in aqueous solution

Thermodynamic and structural properties of a chemically modified DNA-RNA hybrid in which a phosphodiester linkage is replaced by a neutral amide-3 linkage (3'-CH(2)-CONH-5') were investigated using UV melting experiments, molecular dynamics simulations in explicit water, and continuum solvent models. van't Hoff analysis of the experimental UV melting curves suggests that the significant increase of the thermodynamic stability of a 15-mer DNA-RNA with seven alternated amide-3 modifications (+11 degrees C) is mainly due to an increased binding enthalpy. To further evaluate the origin in the observed affinities differences, the electrostatic contribution to the binding free energy was calculated by solving the Poisson-Boltzmann equation numerically. The nonelectrostatic contribution was estimated as the product of a hydrophobic surface tension coefficient and the surface area that is buried upon double strand formation. Structures were taken from 10 ns molecular dynamics simulations computed in a consistent fashion using explicit solvent, counterions, and the particle-mesh Ewald procedure. The present preliminary thermodynamic study suggests that the favorable binding free energy of the amide-3 DNA single strand to the complementary RNA is equally driven by electrostatic and nonpolar contributions to the binding compared to their natural analogues. In addition, molecular dynamics simulations in explicit water were performed on an amide-3 DNA single strand and the corresponding natural DNA. Results from the conformations cluster analysis of the simulated amide-3 DNA single strand ensembles suggest that the 25% of the population sampled within 10 ns has a pre-organized conformation where the sugar C3' endo pucker is favored at the 3'-flanking nucleotides. These structural and thermodynamic features contribute to the understanding of the observed increased affinities of the amide-3 DNA-RNA hybrids at the microscopic level.     

Strong and selective binding of amiloride to thymine base opposite AP sites in DNA duplexes: simultaneous binding to DNA phosphate backbone

Amiloride (N-amidino-3,5-diamino-6-chloro-pyrazinecarboxamide hydrochloride) has two sets of hydrogen-bond forming sites suitable for target nucleotides and the phosphodiester DNA backbone by which a thymine base opposite an abasic site in DNA duplexes can be recognized with high selectivity and affinity, and it is applicable to the fluorescence detection of thymidine-related SNPs (single-nucleotide polymorphisms) of PCR amplification products.     

Dual binding modes of Congo red to amyloid protofibril surface observed in molecular dynamics simulations

Congo red has been used to identify amyloid fibrils in tissues for more than 80 years and is also a weak inhibitor to both amyloid-beta fibril formation and toxicity. However, the specificity of the binding and its inhibition mechanism remain unclear. Using all-atom molecular dynamics simulations with the explicit solvent model, we have identified and characterized two specific binding modes of Congo red molecules to a protofibril formed by an amyloidogenic fragment (GNNQQNY) of the yeast prion protein Sup35. The observation of dual-mode was consistent with the experimentally observed dual-mode binding to Abeta fibrils by a series of compounds similar to Congo red. In the primary mode, Congo red bound to a regular groove formed by the first three residues (GNN) of the beta-strands along the beta-sheet extension direction. Comparative simulations demonstrated that Thioflavin T also bound to the grooves on KLVFFAE protofibril surface. Because of the ubiquitous long grooves on the amyloid fibril surface, we propose that this binding interaction could be a general recognition mode of amyloid fibrils by Congo red, Thioflavin T, and other long flat molecules. In the secondary mode, Congo red bound parallel to the beta-strands on the edge or in the middle of a beta-sheet. The primary binding mode of Congo red and GNNQQNY protofibril was more stable than the secondary mode by -5.7 kcal/mol as estimated by the MM-GBSA method. Detailed analysis suggests that the hydrophobic interactions play important roles for burial of the hydrophobic part of the Congo red molecules. Two potential inhibition mechanisms of disrupting beta-sheet stacking were inferred from the primary mode, which could be exploited for the development of non-peptidic amyloid-specific inhibitors.