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At least 145 records · Page 8Linked to original sources
PubMed2006

Structure, dynamics, and elasticity of free 16s rRNA helix 44 studied by molecular dynamics simulations.

Molecular dynamics (MD) simulations were employed to investigate the structure, dynamics, and local base-pair step deformability of the free 16S ribosomal helix 44 from Thermus thermophilus and of a canonical A-RNA double helix. While helix 44 is bent in the crystal structure of the small ribosomal subunit, the simulated helix 44 is intrinsically straight. It shows, however, substantial instantaneous bends that are isotropic. The spontaneous motions seen in simulations achieve large degrees of bending seen in the X-ray structure and would be entirely sufficient to allow the dynamics of the upper part of helix 44 evidenced by cryo-electron microscopic studies. Analysis of local base-pair step deformability reveals a patch of flexible steps in the upper part of helix 44 and in the area proximal to the bulge bases, suggesting that the upper part of helix 44 has enhanced flexibility. The simulations identify two conformational substates of the second bulge area (bottom part of the helix) with distinct base pairing. In agreement with nuclear magnetic resonance (NMR) and X-ray studies, a flipped out conformational substate of conserved 1492A is seen in the first bulge area. Molecular dynamics (MD) simulations reveal a number of reversible alpha-gamma backbone flips that correspond to transitions between two known A-RNA backbone families. The flipped substates do not cumulate along the trajectory and lead to a modest transient reduction of helical twist with no significant influence on the overall geometry of the duplexes. Despite their considerable flexibility, the simulated structures are very stable with no indication of substantial force field inaccuracies.

Base Pairing↗
PubMed1994

Lagrangian molecular dynamics using selected conformational degrees of freedom, with application to the pseudorotation dynamics of furanose rings.

Using internal conformational degrees of freedom for biopolymers as natural variables, and introducing a Lagrangian dynamics approach, one can simulate time-dependent processes over a much longer time scale than in classical Newtonian molecular dynamics (MD) techniques. Two factors contribute to this: a substantial reduction in the number of degrees of freedom and a very large increase in the size of the time step. We present the Lagrangian equations of motion for repuckering transitions in model furanose (F), ribose (R), and 2'-deoxyribose (dR) ring systems using the pseudorotation phase angle as the single dynamic variable. As in most Lagrangian analyses, the effective masses for the R and dR models are dependent on conformation, and we test the behavior of this variable mass (VM) model. Since the variation in effective mass is small, the VM model is compared with a simplified constant mass (CM) model, which is shown to be an excellent approximation. The equations of motion for the CM and VM models are integrated with the leapfrog and the iterative leapfrog algorithms, respectively. The Lagrangian dynamics approach reduces the number of degrees of freedom from about 40 to 1, and allows the use of time steps on the order of 20 fs, about an order of magnitude greater than is used in conventional MD simulations.

Biopolymers↗
PubMed2004

A hybrid method of molecular dynamics and harmonic dynamics for docking of flexible ligand to flexible receptor.

We have developed a new docking method to consider receptor flexibility, a hybrid method of molecular dynamics and harmonic dynamics. The global motions of the whole receptor were approximately introduced into those of the receptor in the docking simulation as harmonic dynamics. On the other hand, the local flexibility of the side chains was also considered by conventional molecular dynamics. We confirmed that this new method can reproduce the fluctuations of the whole receptor by making a comparison of the directions and amplitudes of the global fluctuations. Then this method was applied to the docking of HIV-1 protease and its ligand. As a result, we observed a docking process where the ligand enters into the binding pocket well, which implies that this method is effective enough to reproduce a molecular complex formation.

Algorithms↗
PubMed1992

Molecular dynamics studies of a DNA-binding protein: 2. An evaluation of implicit and explicit solvent models for the molecular dynamics simulation of the Escherichia coli trp repressor.

Although aqueous simulations with periodic boundary conditions more accurately describe protein dynamics than in vacuo simulations, these are computationally intensive for most proteins. Trp repressor dynamic simulations with a small water shell surrounding the starting model yield protein trajectories that are markedly improved over gas phase, yet computationally efficient. Explicit water in molecular dynamics simulations maintains surface exposure of protein hydrophilic atoms and burial of hydrophobic atoms by opposing the otherwise asymmetric protein-protein forces. This properly orients protein surface side chains, reduces protein fluctuations, and lowers the overall root mean square deviation from the crystal structure. For simulations with crystallographic waters only, a linear or sigmoidal distance-dependent dielectric yields a much better trajectory than does a constant dielectric model. As more water is added to the starting model, the differences between using distance-dependent and constant dielectric models becomes smaller, although the linear distance-dependent dielectric yields an average structure closer to the crystal structure than does a constant dielectric model. Multiplicative constants greater than one, for the linear distance-dependent dielectric simulations, produced trajectories that are progressively worse in describing trp repressor dynamics. Simulations of bovine pancreatic trypsin were used to ensure that the trp repressor results were not protein dependent and to explore the effect of the nonbonded cutoff on the distance-dependent and constant dielectric simulation models. The nonbonded cutoff markedly affected the constant but not distance-dependent dielectric bovine pancreatic trypsin inhibitor simulations. As with trp repressor, the distance-dependent dielectric model with a shell of water surrounding the protein produced a trajectory in better agreement with the crystal structure than a constant dielectric model, and the physical properties of the trajectory average structure, both with and without a nonbonded cutoff, were comparable.

Amino Acid Sequence↗
PubMed2006

Methyl dynamics for understanding hydrophobic core packing of dynamically different motifs of double-stranded RNA binding domain of protein kinase R.

Double-stranded RNA binding domains of human protein kinase R (dsRBD-PKR) regulate distinct cellular functions and the fate of an RNA molecule in the cell. This highly homologous domains present in multiple copies in a number of species, exhibit individual and specific functional specificity. Number of NMR and X-ray crystallographic structural studies reveals that such domains take a common alpha-beta-beta-beta-alpha tertiary fold. However, the functional specificities of these domains could be due to the dynamics of the individual amino acid residues, as has been shown earlier in the case of backbone dynamics of 15N-1H of dsRNA binding motifs (dsRBMs) of human protein kinase R (PKR) (Nanduri S, Rahman F, Williams BRG, Qin J. EMBO J 2000;19:5567-5574). To further investigate if the differences in dynamics of the two dsRBMs are restricted to only backbone, or if the side-chain motions are also different to the extent of influencing their packing of the two hydrophobic cores, we have investigated the methyl group dynamics using 13C-methyl relaxation measurements. The results show that the hydrophobic core of dsRBM1 is more tightly packed than dsRBM2, and it seems to undergo less fast scale motions in the subnanosecond regime.

Amino Acid Substitution↗
PubMed1996

Microscopic and Macroscopic Dynamic Interface Shapes and the Interpretation of Dynamic Contact Angles.

We have studied shapes of dynamic fluid interfaces at distances </=1700 µm from the moving contact line at capillary numbers (Ca) ranging from 10(-3) to 10(-1). Near the moving contact line where viscous deformation is important, an analysis valid to O(1) in Ca describes the shape of the fluid interface. Static capillarity should describe the interface shape far from the contact line. We have quantitatively determined the extent of the regions described by the analysis with viscous deformation and by a static shape as a function of Ca. We observe a third portion of the interface between the two regions cited above, which is not described by either the analysis with viscous deformation or a static shape. In this third region the interface shape is controlled by viscous and gravitational forces of comparable magnitude. We detect significant viscous deformation even far from the contact line at Ca approximately > 0.01. Our measured dynamic contact angle parameter extracted by fitting the analysis with viscous deformation to the shape near the moving contact line coincides with the contact angle of the static-like shape far from the contact line. We measure and explain the discrepancy between this dynamic contact angle parameter and the apparent contact angles based on meniscus or apex heights. Our observations of viscous effects at large distances from the contact line have implications for dynamic contact angle measurements in capillary tubes.

Journal Article↗
PubMed1999

Dynamic Surface Tension Measurement with a Dynamic Wilhelmy Plate Technique.

An experimental method called dynamic Wilhelmy plate technique (DWPT) for studying dynamic surface tension was designed in this study. A diffusion-controlled model corresponding to the initial and boundary conditions of this method was proposed. Dynamic surface tension of Triton X-100 and SDS was measured with this technique and analyzed with the proposed model. The calculated diffusion coefficients for the short- and long-time approximations are 3.7 x 10(-6) and 0.97 x 10(-6) cm(2)/s for Triton X-100 and 4.6 x 10(-6) and 0.79 x 10(-6) cm(2)/s for SDS, respectively. The predicted dynamic surface tension with these diffusion coefficients for the simultaneously generated aqueous/air interfaces is in good agreement with the drop mass technique. Another diffusion controlled model that considers the energy barrier at the aqueous/air interface was also proposed in this study. The calculated energy barriers are in the range of 4.1-5.7 RT for Triton X-100 and 6.5-8.0 RT for SDS. Copyright 1999 Academic Press.

Journal Article↗
PubMed1980

Dynamic scintigraphy with high temporal resolution. Phase dynamic studies of rapid periodical processes.

The theory and general method of construction of the phase dynamic studies of rapid periodical processes with high temporal resolution is described briefly. Moreover, problems are discussed that are associated with the introduction of external pulses into dynamic studies in LIST-mode, the spatial and temporal reconstruction from LIST-mode, the computer's construction of phase dynamic studies, the selection of correct cycles, the creation of phase histograms and processing of the phase studies. The method is illustrated by a general program LIST leads to PHASE DYNAM. STUDY created for Clincom apparatus. In addition to the general method, there is mentioned here the modification of the simplified procedure--a well-known EKG-gated method. Some aspects of the method are documented by the results of phantom measurement and clinical examinations.

Electrocardiography↗
PubMed1978

New aspects of cerebrospinal fluid dynamics in humans investigated by sequential gamma camera cisternography, with data evaluation by the digital multichannel analyzer. Part 4: A unifying criterion of the development of hydrocephalic syndrome. Its dynamic basis.

In the final part of this series we present all of the clinical material, and the patients are classified by different cisternographic syndromes on the dynamic basis offered for our method: dynamic disconnection between ventricular system and basal cisterns, brain atrophy, initial dynamic decompensation or prehydrocephalus, communicating hydrocephalus with and without epicortical fluid circulation. A nomogram method for clinical estimation of CSF production based on the mathematical properties of our analysis of the ventricular reflux is proposed. The different normal and pathological characteristics of fluid movements in the spinal canal are given, and their importance as signs of turbulence in the posterior fossa are emphasized. Different aspects of the dynamics of CSF production are shown and discussed, and an evolving conception of hydrocephalus development is presented.

Adolescent↗
PubMed2006

Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings.

We examined how static and dynamic deviations from the idealized A-form helix propagate into errors in the principal order tensor parameters determined using residual dipolar couplings (rdcs). A 20-ns molecular dynamics (MD) simulation of the HIV-1 transactivation response element (TAR) RNA together with a survey of spin relaxation studies of RNA dynamics reveals that pico-to-nanosecond local motions in non-terminal Watson-Crick base-pairs will uniformly attenuate base and sugar one bond rdcs by approximately 7%. Gaussian distributions were generated for base and sugar torsion angles through statistical comparison of 40 RNA X-ray structures solved to <3.0 A resolution. For a typical number (>or=11) of one bond C-H base and sugar rdcs, these structural deviations together with rdc uncertainty (1.5 Hz) lead to average errors in the magnitude and orientation of the principal axis of order that are <9% and <4 degrees, respectively. The errors decrease to <5% and <4 degrees for >or=17 rdcs. A protocol that allows for estimation of error in A-form order tensors due to both angular deviations and rdc uncertainty (Aform-RDC) is validated using theoretical simulations and used to analyze rdcs measured previously in TAR in the free state and bound to four distinct ligands. Results confirm earlier findings that the two TAR helices undergo large changes in both their mean relative orientation and dynamics upon binding to different targets.

Base Pairing↗
PubMed2006

Molecular dynamics simulations of trehalose as a 'dynamic reducer' for solvent water molecules in the hydration shell.

Systematic computational work for a series of 13 disaccharides was performed to provide an atomic-level insight of unique biochemical role of the alpha,alpha-(1-->1)-linked glucopyranoside dimer over the other glycosidically linked sugars. Superior osmotic and cryoprotective abilities of trehalose were explained on the basis of conformational and hydration characteristics of the trehalose molecule. Analyses of the hydration number and radial distribution function of solvent water molecules showed that there was very little hydration adjacent to the glycosidic oxygen of trehalose and that the dynamic conformation of trehalose was less flexible than any of the other sugars due to this anisotropic hydration. The remarkable conformational rigidity that allowed trehalose to act as a sugar template was required for stable interactions with hydrogen-bonded water molecules. Trehalose made an average of 2.8 long-lived hydrogen bonds per each MD step, which was much larger than the average of 2.1 for the other sugars. The stable hydrogen-bond network is derived from the formation of long-lived water bridges at the expense of decreasing the dynamics of the water molecules. Evidence for this dynamic reduction of water by trehalose was also established based on each of the lowest translational diffusion coefficients and the lowest intermolecular coulombic energy of the water molecules around trehalose. Overall results indicate that trehalose functions as a 'dynamic reducer' for solvent water molecules based on its anisotropic hydration and conformational rigidity, suggesting that macroscopic solvent properties could be modulated by changes in the type of glycosidic linkages in sugar molecules.

Computer Simulation↗
PubMed2006

Dynamic cine-CT angiography for the evaluation of the thoracic aorta; insight in dynamic changes with implications for thoracic endograft treatment.

OBJECTIVE: Thoracic aneurysm preoperative imaging is performed using static techniques without consideration of normal aortic dynamics. Improved understanding of the native aortic environment into which thoracic endografts are placed may aid in device selection. It is unclear what comprises normal thoracic aortic pulsatility. We studied these phenomena dynamically using ECG-gated 64-slice CTA. METHODS: Maximum diameter and area change per cardiac cycle was measured at surgically relevant anatomic thoracic landmarks in ten patients; 1.0 cm proximal and distal to the subclavian artery, 3.0 cm distal to the subclavian artery, and 3.0 cm proximal to the celiac trunk. Data was acquired using a novel ECG-gated dynamic 64-slice CT scanner during a single breath hold with a standard radiation dose and contrast load. Eight gated data sets, covering the cardiac cycle were reconstructed, perpendicular to the central lumen. RESULTS: There is impressive change in both maximum diameter and area in the thoracic aorta during the cardiac cycle. Mean maximum diameter changes of greater than 10% are observed in the typical sealing zones of commercially available endografts corresponding to diameter increases of up to 5mm. Aortic area increases by over 5% per cardiac cycle. CONCLUSIONS: ECG-gated dynamic CTA with standard radiation dose is feasible on a 64-slice scanner and provides insight into (patho) physiology of thoracic aortic conformational changes. Clinicians typically oversize thoracic endografts by 10%. With aortic pulsatility resulting in diameter changes of up to 17.8%, the potential exists for endograft undersizing, graft migration, intermittent type I endoleak, and poor patient outcome. Furthermore, aortic pulsatility is not evenly distributed, and non-circular stentgraft designs should be considered in the future since aortic distension in the aneurysm neck is not evenly distributed.

Angioplasty↗
PubMed2005

What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysis.

Molecular dynamics simulations of the structurally homologous proteins TNfn3 and FNfn10 have been used to investigate the contributions to side-chain dynamics measured by NMR relaxation experiments. The results reproduce the variation in core side-chain dynamics observed by NMR and highlight the relevance of anharmonic motion and transitions between local minima for explaining NMR side-chain order parameters. A method is described for calculating converged order parameters by use of replica exchange molecular dynamics in conjunction with an implicit solvent model. These simulations allow the influence of various factors, such as the flexibility of side-chains and their free volume, on the mobility to be tested by perturbing the system. Deletion mutations are found to have the largest effect on the more densely packed FNfn10. Some counterintuitive effects are seen, such as an increase in order parameters close to deletion mutation sites, but these can be rationalized in terms of direct interactions with the modified side-chains. A statistical analysis of published order parameters supports the conclusions drawn from the simulations.

Amino Acids↗
PubMed2003

Molecular dynamics simulation of protein folding by essential dynamics sampling: folding landscape of horse heart cytochrome c.

A new method for simulating the folding process of a protein is reported. The method is based on the essential dynamics sampling technique. In essential dynamics sampling, a usual molecular dynamics simulation is performed, but only those steps, not increasing the distance from a target structure, are accepted. The distance is calculated in a configurational subspace defined by a set of generalized coordinates obtained by an essential dynamics analysis of an equilibrated trajectory. The method was applied to the folding process of horse heart cytochrome c, a protein with approximately 3000 degrees of freedom. Starting from structures, with a root-mean-square deviation of approximately 20 A from the crystal structure, the correct folding was obtained, by utilizing only 106 generalized degrees of freedom, chosen among those accounting for the backbone carbon atoms motions, hence not containing any information on the side chains. The folding pathways found are in agreement with experimental data on the same molecule.

Algorithms↗
PubMed2003

Interdomain dynamics and ligand binding: molecular dynamics simulations of glutamine binding protein.

Periplasmic binding proteins from Gram-negative bacteria possess a common architecture, comprised of two domains linked by a hinge region, a fold which they share with the neurotransmitter-binding domains of ionotropic glutamate receptors (GluRs). Glutamine-binding protein (GlnBP) is one such protein, whose crystal structure has been solved in both open and closed forms. Multi-nanosecond molecular dynamics simulations have been used to explore motions about the hinge region and how they are altered by ligand binding. Glutamine binding is seen to significantly reduce inter-domain motions about the hinge region. Essential dynamics analysis of inter-domain motion revealed the presence of both hinge-bending and twisting motions, as has been reported for a related sugar-binding protein. Significantly, the influence of the ligand on GlnBP dynamics is similar to that previously observed in simulations of rat glutamate receptor (GluR2) ligand-binding domain. The essential dynamics analysis of GlnBP also revealed a third class of motion which suggests a mechanism for signal transmission in GluRs.

Binding Sites↗
PubMed2003

Comparison of the static, dynamic and static-dynamic pressurised liquid extraction modes for the removal of nitrated polycyclic aromatic hydrocarbons from soil with on-line filtration-preconcentration.

The three operational modes of pressurised liquid extraction (PLE) (namely, static, dynamic and static-dynamic) have been applied for the extraction of nitrated polycyclic aromatic hydrocarbons from both spiked and natural contaminated soils. A comparison of the three modes in terms of experimental set-up used, extraction time needed for total removal of the analytes and precision has been carried out. The use of a flow-injection manifold as interface between every pressurised extractor and a filtration-preconcentration system has allowed the partial automation of the proposed approaches. Efficiencies close to 100% have been provided by the three operational modes. However, the static-dynamic mode has been proved as the most suitable alternative providing the shortest extraction time (25 min) versus the static (30 min) and the dynamic (50-70 min) modes. Gas chromatography with MS-MS ion preparation mode has been used providing both high selectivity (no interferences were observed) and sensitivity (detection limits of low pg). The comparison of the proposed approaches with the reference method 3540 of the US Environmental Protection Agency (EPA) has shown that both methods provide similar efficiencies with an important shortening in the extraction time (25-70 min by PLE versus 24 h by the EPA method). The use of water as leaching agent has avoided the use of organic solvents providing an environmentally friendly method.

Filtration↗
PubMed1999

Long-term molecular dynamics simulation of copper azurin: structure, dynamics and functionality.

A long-term molecular dynamics simulation (1.1 ns), at 300 K, of fully hydrated azurin has been performed to put into relationship the protein dynamics to functional properties with particular attention to those structural elements involved in the electron transfer process. A detailed analysis of the root mean square deviations and fluctuations and of the intraprotein H-bonding pattern has allowed us to demonstrate that a rigid arrangement of the beta-stranded protein skeleton is maintained during the simulation run, while a large mobility is registered in the solvent-exposed connecting regions (turns) and in the alpha-helix. Moreover, the structural elements, likely involved in the electron transfer path, show a stable H-bonding arrangement and low fluctuations. Analysis of the dynamical cross-correlation map has revealed the existence of correlated motions among residues connected by hydrogen bonds and of correlated and anti-correlated motions between regions which are supposed to be involved in the functional process, namely the hydrophobic patch and the regions close to the copper reaction center. The results are briefly discussed also in connection to the current through-bond tunneling model for the electron transfer process. Finally, a comparison with the structural and the dynamical behaviour of plastocyanin, whose structure and functional role are very similar to those of azurin, has been performed.

Journal Article↗
PubMedDate not supplied

Nonlinear dynamic perspectives on dynamic force microscopy.

Dynamic force microscopy (DFM) utilizes the dynamic response of a resonating probe tip as it approaches and retracts from a sample to measure the topography and material properties of a nanostructure. We present recent results based on nonlinear dynamical systems theory, computational continuation techniques and detailed experiments that yield new perspectives and insights into DFM.A dynamic model including van der Waals and Derjaguin-Müller-Toporov contact forces demonstrates that periodic solutions can be represented as a catastrophe surface with respect to the approach distance and excitation frequency. Turning points on the surface lead to hysteretic amplitude jumps as the tip nears/retracts from the sample. New light is cast upon sudden global changes that occur in the interaction potential at certain gap widths that cause the tip to "stick" to, or tap irregularly the sample. Experiments are performed using a tapping mode tip on a graphite sample to verify the predictions.

Journal Article↗