Comparative Molecular Dynamics Study Research Articles

Response of ultrathin metal films to ultrafast laser irradiation: A comparative molecular-dynamics study

Using molecular-dynamics computer simulation, we study the materials processes in ultrathin metal films induced by ultrafast laser irradiation. We investigate four different metals (Al, Cu, Ti, W), which vary widely in their cohesive energy, melting temperature, bulk modulus, and crystal structure. Despite these variations, we find that the same materials processes are induced in these films: With increasing laser fluence, the film melts, voids are formed, the film tears (spallation), and finally fragments to form a multitude of clusters. When the energy transfer starting the process is scaled to the cohesive energy of the material, the thresholds of these processes adopt similar – but not identical – values.

The role of phosphorylation on the structure and dynamics of phospholamban: A model from molecular simulations

Phospholamban (PLB) is a small membrane protein that regulates the activity of the calcium ATP-ase in the cardiac, slow-twitch, and smooth muscle sarcoplasmic reticulum through the reversible phosphorylation of Ser16. We present here a comparative molecular dynamics study of unmodified and phosphorylated PLB immersed in a phospholipid membrane. The study has been performed under different ionic strength conditions, using the NMR structures of two PLB variants determined in mixed organic solvent and dodecylphosphocholine micelles. The simulations indicate that all PLB forms studied display a highly dynamic behavior of the N-terminal cytoplasmic moiety, with a decrease of its helical content in the phosphorylated forms. The cytoplasmic domain undergoes large collective motions sampling conformations parallel as well as perpendicular to the membrane surface in all the simulations. The transmembrane domain retains a tightly folded helical conformation with a small tilt with respect to the membrane plane probably induced by the presence of Asn30 and Asn34 within the hydrophobic environment. Furthermore, the phosphoric group on Ser16 establishes transient electrostatic interactions with the phospholipid heads. We propose a model in which phosphorylation diminishes the probability of interactions of PLB with residues near Lys400 in the SERCA pump, thus relieving its inhibition.

A comparative study of molecular dynamics in Cartesian and in internal coordinates: Dynamical instability in the latter caused by nonlinearity of the equations of motion

The stability of a general molecular dynamics (MD) integration scheme is examined for simulations in generalized (internal plus external) coordinates (GCs). An analytic expression is derived for the local error in energy during each integration time step. This shows that the explicit dependence of the mass-matrix on GCs, which makes the system's Lagrange equations of motion nonlinear, causes MD simulations in GCs to be less stable than those in Cartesian coordinates (CCs). In terms of CCs, the corresponding mass-matrix depends only on atomic masses and thus atomistic motion is subject to the linear Newton equations, which makes the system more stable. Also investigated are two MD methods in GCs that utilize nonzero elements of the vibrational spectroscopic B-matrices. One updates positions and velocities in GCs that are iteratively adjusted so as to conform to the velocity Verlet equivalent in GCs. The other updates positions in GCs and velocities in CCs that are adjusted to satisfy the internal constraints of the new constrained WIGGLE MD scheme. The proposed methods are applied to an isolated n-octane molecule and their performances are compared with those of several CCMD schemes. The simulation results are found to be consistent with the analytic stability analysis. Finally, a method is presented for computing nonzero elements of B-matrices for external rotations without imposing the Casimir-Eckart conditions.

A Comparative Molecular Dynamics Study of Thermophilic and Mesophilic Ribonuclease HI Enzymes

We studied a pair of homologous thermophilic and mesophilic ribonuclease HI enzymes by molecular dynamics simulations. Each protein was subjected to three 5 ns simulations in explicit water at both 310 K and 340 K. The thermophilic enzyme showed larger overall positional fluctuations at both temperatures, while only the mesophilic enzyme at the higher temperature showed significant instability. When the temperature is changed, the relative flexibility of different local segments on the two proteins changed differently. Principal component analysis showed that the simulations of the two proteins explored largely overlapping regions in the conformational space. However, at 340 K, the collective structure variations of the thermophilic protein are different from those of the mesophilic protein. Our results, although not in accordance with the view that hyperthermostability of proteins may originate from their conformational rigidity, are consistent with several recent experimental and simulation studies which showed that thermophilic proteins may be conformationally more flexible than their mesophilic counterparts. The decorrelation between conformational rigidity and hyperthermostability may be attributed to the temperature dependence and long range nature of electrostatic interactions that play more important roles in the structural stability of thermophilic proteins.

Interaction of the Sugars Trehalose, Maltose and Glucose with a Phospholipid Bilayer: A Comparative Molecular Dynamics Study

Molecular dynamics simulations are used to investigate the interaction of the sugars trehalose, maltose, and glucose with a phospholipid bilayer at atomic resolution. Simulations of the bilayer in the absence or in the presence of sugar (2 molal concentration for the disaccharides, 4 molal for the monosaccharide) are carried out at 325 and 475 K. At 325 K, the three sugars are found to interact directly with the lipid headgroups through hydrogen bonds, replacing water at about one-fifth to one-quarter of the hydrogen-bonding sites provided by the membrane. Because of its small size and of the reduced topological constraints imposed on the hydroxyl group locations and orientations, glucose interacts more tightly (at identical effective hydroxyl group concentration) with the lipid headgroups when compared to the disaccharides. At high temperature, the three sugars are able to prevent the thermal disruption of the bilayer. This protective effect is correlated with a significant increase in the number of sugar-headgroups hydrogen bonds. For the disaccharides, this change is predominantly due to an increase in the number of sugar molecules bridging three or more lipid molecules. For glucose, it is primarily due to an increase in the number of sugar molecules bound to one or bridging two lipid molecules.

Selected biologically relevant ions at the air/water interface: A comparative molecular dynamics study

Interfacial behavior of selected biologically and technologically relevant ions is studied using molecular dynamics simulations employing polarizable potentials. Propensities of choline, tetraalkylammonium (TAA), and sodium cations, and sulfate and chloride anions for the air/water interface are analyzed by means of density profiles. Affinity of TAA ions for the interface increases with their increasing hydrophobicity. Tetramethylammonium favors bulk solvation, whereas cations with propyl and butyl chains behave as surfactants. The choice of counter-anions has only a weak effect on the behavior of these cations. For choline, sodium, chloride and sulfate, the behavior at the air/water interface was compared to the results of our recent study on the segregation of these ions at protein surfaces. No analogy between these two interfaces in terms of ion segregation is found.

Comparative Molecular Dynamics Study of Lipid Membranes Containing Cholesterol and Ergosterol

Sterol molecules are essential for maintaining the proper structure and function of eukaryotic cell membranes. The influence of cholesterol (the principal sterol of higher animals) on the lipid bilayer properties was extensively studied by both experimental and simulation methods. In contrast, the effect of ergosterol (the principal fungal sterol) on the membrane structure and dynamics is much less recognized. This work presents the results of comparative molecular dynamics simulation of the hydrated dimyristoylphosphatidylcholine bilayer containing ∼25 mol % of cholesterol or ergosterol. A detailed analysis of the molecular properties (e.g., bilayer thickness, lipid order, diffusion, intermolecular interactions, etc.) of both sterol-induced liquid-ordered membrane phases is presented. Presence of sterols in the membrane significantly changes its property, especially fluidity and molecular packing. Moreover, in accordance with the experiments, our calculations show that, compared to cholesterol, ergosterol has higher ordering effect on the phospholipid acyl chains. This different influence on the properties of the lipid bilayer stems from differences in conformational freedom of sterol side chains. Additionally, obtained models of lipid membranes containing human and fungal sterols, constituting the result of our work, can be also utilized in other chemotherapeutic studies on interaction of selected ligands (e.g., antifungal compounds) with membranes.

Role of phosphorylated Thr160 for the activation of the CDK2/Cyclin A complex

The enzymatic activity of the CDK2/Cyclin A complex increases upon the specific phosphorylation of Thr160@CDK2. In the present study, we have performed a comparative molecular dynamics (MD) study of models of the complex CDK2/Cyclin A/Substrate, which differ for the presence or absence of the phosphate group bound to Thr160. The models are based on two X-ray structures available for CDK2/CyclinA and pCDK2/CyclinA/Substrate complexes. In this way, we analyze the influence of the phosphorylated Thr160 (pThr160) on both the flexibility of CDK2 activation loop (AL) and substrate binding in CDK2. Our calculations point to a decreased flexibility of the AL in the phosphorylated model, in fairly good agreement with experimental data, and to a key role of pThr160 for substrate recognition and stability. Multiple alignments of the CDKs sequences point to the very high conservation of the AL sequence among the CDKs, thus extending our results to all CDKs.

Increased Flexibility as a Strategy for Cold Adaptation: A COMPARATIVE MOLECULAR DYNAMICS STUDY OF COLD- AND WARM-ACTIVE URACIL DNA GLYCOSYLASE

Uracil DNA glycosylase (UDG) is a DNA repair enzyme in the base excision repair pathway and removes uracil from the DNA strand. Atlantic cod UDG (cUDG), which is a cold-adapted enzyme, has been found to be up to 10 times more catalytically active in the temperature range 15-37 degrees C as compared with the warm-active human counterpart. The increased catalytic activity of cold-adapted enzymes as compared with their mesophilic homologues are partly believed to be caused by an increase in the structural flexibility. However, no direct experimental evidence supports the proposal of increased flexibility of cold-adapted enzymes. We have used molecular dynamics simulations to gain insight into the structural flexibility of UDG. The results from these simulations show that an important loop involved in DNA recognition (the Leu(272) loop) is the most flexible part of the cUDG structure and that the human counterpart has much lower flexibility in the Leu(272) loop. The flexibility in this loop correlates well with the experimental k(cat)/K(m) values. Thus, the data presented here add strong support to the idea that flexibility plays a central role in adaptation to cold environments.

A comparative molecular dynamics study of copper trench fill properties between Ta and Ti barrier layers

The copper atoms deposition on tantalum diffusion barrier layer in a damascene process was studied using molecular dynamics simulation with the embedded atom method (EAM) as interaction potential for the present alloy metal system which is based on invariance-preserving alloy model. The present results are discussed in terms of void formation, coverage percentage and alloy fraction. The effects of different process parameters on the trench-filling morphologies and microstructures including incident energies of depositing atoms and substrate temperatures were investigated. Comparing with Ti diffusion barrier under the same process parameters, it is found that due to better thermal stability that significant improvement in coverage percentage can be obtained using the tantalum barrier layer, especially at high incident energies and high substrate temperatures.

Comparative molecular dynamics study of ether- and ester-linked phospholipid bilayers

The lipid membranes found in archaea have high bilayer stability and low permeability. The molecular structure of their constituent lipids is characterized by ether-linked, branched hydrophobic chains, whereas the conventional lipids obtained from eukaryotic or eubacterial sources have ester linked straight chains. In order to elucidate the influence of the ether linkage, instead of an ester one, on the physical properties of the lipid bilayers, we have carried out comparative 10 ns molecular dynamics simulations of diphytanyl phosphatidylcholine (ether-DPhPC) and diphytanoyl phosphatidylcholine (ester-DPhPC) bilayers in water, respectively. We analyze bilayer structures, hydration of the lipids, membrane dipole potentials, and free energy profiles of water and oxygen across the bilayers. We observe that the membrane dipole potential for the ether-DPhPC bilayer, which arises mainly from the ether linkage, is about half of that of the ester-DPhPC. The calculated free energy barrier for a water molecule in the ether-DPhPC bilayer system is slightly higher than that in the ester-DPhPC counterpart, which is in accord with experimental data.

The Sequence Dependence of Fiber Organization. A Comparative Molecular Dynamics Study of the Islet Amyloid Polypeptide Segments 22–27 and 22–29

Amyloid fiber formation and the possible polymorphism of molecular arrangements depend on the polypeptide length and composition. Here, we seek the chemical clues underlying these processes. Our starting point is based on the experimental observation that some short peptide segments are able to develop fibers that are very similar to those of their original parent proteins. We focus our study on the NFGAILSS peptide, derived from the human islet amyloid polypeptide (residues 22–29). This peptide turned out to be a perfect example, illustrating the fact that the amyloid microscopic organization is highly complex, rather than simply involving hydrogen bond formation. Furthermore, obtaining a reliable molecular model has allowed us to analyze the differences between the amyloid structure we have obtained for this peptide and that obtained for the previously studied, two residues shorter, segment (residues 22–27, NFGAIL). This comparative study yields some clues about chemical events that govern the aggregation of proteins into oriented fibers, such as molecular packing between sheets and the degree of interaction specificity. We characterize the important role played by the hydrophobic and aromatic residues in the inter-sheet association and present new approaches toward the understanding of the nature of events that are likely to take place during fibril formation. These include analysis of interaction patterns derived from specific sheet-associated packing.

Comparative study of quasiharmonic lattice dynamics, molecular dynamics and Debye model applied to MgSiO 3 perovskite

We consider three independent methodologies for calculating thermal equation of state (EOS) of the major earth-forming mineral, orthorhombic MgSiO 3 perovskite: molecular dynamics (MD), lattice dynamics (LD) and Debye model (DM). Using the most recent developments in the GULP code, we derive a new interatomic potential, which is demonstrated to be extremely robust at both high temperatures and high pressures. With this potential we construct a quasiharmonic self-consistent DM based on elastic properties of the crystal, and compare its results with results of more rigorous LD and MD simulations with the same potential model. We show that the DM reproduces quite accurately harmonic constant-volume heat capacity above 500 K, but gives thermal expansion and Grüneisen parameter ( γ) that are too small. We conclude that MgSiO 3 perovskite is not a Debye-like solid, in contrast to what has often been assumed in geophysical literature. Acoustic γ, often used in geophysical studies, are a very crude approximation to the true γ. To obtain good accuracy, one needs to know the γ( V) function more accurately than the DM can give. However, analytical functions, given by the Debye theory, are useful for fitting thermal expansion and related parameters at elevated temperatures. A common assumption that q= d ln γ/ d ln V is constant is found to be inadequate: in fact, q varies strongly with volume and can reach negative values towards the base of the lower mantle. This can be relevant for discussion of the anomalous properties of the core-mantle boundary (D″) layer. Comparison of results of LD and MD indicates importance of intrinsic anharmonic contributions in the thermal expansion and γ. Therefore, MD is the most suitable technique for simulating minerals at the Earth’s mantle conditions.

The binding mechanism of urea, hydroxamic acid and N-( N-butyl)-phosphoric triamide to the urease active site. A comparative molecular dynamics study

Molecular dynamics (MD) calculations have been performed on the active site of urease from Klebsiella aerogenes and its adducts with urea, hydroxamic acid and N-( n-butyl)-phosphoric triamide (NBPT). The catalytic nickel atoms were explicitly included in all the simulations. The nickel atoms, as shown by X-ray analysis, are linked by a carbamate bridge. Average MD structures were calculated starting from the X-ray structure of the urease active site and docking the ligand and the inhibitors from different starting conformations. The urea molecule binds to only one of the Ni atoms, the hydroxamic acid behaves like a monodentate or a bidentate ligand depending on the pH, and NBPT coordinates both the Ni centers and a carbamate residue via the formation of and hydrogen bond thus acting as a tridentate ligand. The proposed binding mechanisms agree with known data about hydroxamic and urea complexes with urease.

Comparative molecular dynamics study of the seven-helix bundle arrangement of G-protein coupled receptors

A comparative molecular dynamics study has been performed on the seven-helix bundle arrangement of seven G-protein coupled receptors (GPCRs). They are hamster α 1 B − , human α 2− , β 2 −-adrenergic, human D 2-dopaminergic, human 5-HT 1A-serotoninergic, human ml-muscarinic receptors and bovine rhodopsin. Starting from a rhodopsin-like input structure and a bacteriorhodopsin-like input structure, a similar arrangement of the averaged helix bundles was obtained. This may be due to the topography of some fundamental polar positions in both the input structures which is substantially the same and dictates, through the establishment of similar H-bonding networks, the helix-helix packing. By comparing the averaged structures and the packing interaction parameters obtained for the GPCRs considered with that of bacteriorhodopsin, we observe that the GPCRs share a similar packing arrangement of their transmembrane helix bundles which differs from that of bacteriorhodopsin. The results obtained from the quantitative and comparative molecular modelling of the GPCRs constitute an important preliminary step in a general understanding of both structure-function and structure activity-selectivity relationships in these proteins, at the molecular level.

Studies of solvated ion motion: Molecular dynamics results for dilute aqueous solutions of alkali and halide ions

A comparative molecular dynamics study of the motion of the alkali cations Li+, Na+, and K+ and the halide anions F− and Cl− in the Stillinger–Rahman revised central field model for water is presented.