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PubMed2005

Dynamic modulation of visual detection by auditory cues in spatial neglect.

One of the most constant findings of studies about selective attention is that detection of visual stimuli is enhanced when a visual cue is presented at the position of the upcoming target. In healthy participants, comparable benefits were reported when the cue was presented in a different modality than the target. The aim of this study was to examine spatial and temporal dynamics of visual attention following auditory cues in patients with spatial neglect. Twelve healthy subjects and five patients with left-sided neglect were asked to react to a small vertical line presented randomly at one of four positions. The target appeared 150 or 1000 ms after an auditory cue that was either static (continuous 380 Hz tone presented to the left or right ear) or dynamic (380 Hz tone moving from the left to the right ear or vice versa). The reaction time pattern of healthy participants was unaffected by the different tones. In contrast, reaction times of neglect patients were significantly faster to left targets following a dynamic tone moving from right to left in comparison to a tone moving from left to right. Interestingly, static unilateral tones modulated visual attention of neglect patients to a lesser degree than dynamic tones. The modulation of visual attention by dynamic auditory cues was of short duration and disappeared after 1000 ms. These results demonstrate a fast automatic shift of spatial attention in the direction of a moving tone, suggesting strong dynamic links between visual and auditory attention in patients with a severe spatial deficit.

Acoustic Stimulation↗
PubMed2004

Clinical implementation of dynamic and step-and-shoot IMRT to treat prostate cancer with high risk of pelvic lymph node involvement.

BACKGROUND AND PURPOSE: Two systems have been developed for treating patients with locally advanced prostate cancer using intensity-modulated radiotherapy (IMRT): one using dynamic multi-leaf collimator delivery and the other using step-and-shoot. This paper describes the clinical implementation of these two techniques, and presents results from the first 14 patients treated in a clinical setting (nine dynamic, five step-and-shoot). PATIENTS AND METHODS: Dynamic treatments were planned using Corvus, and step-and-shoot using Helax-TMS; all were delivered using Elekta accelerators. Prior to the first clinical treatments, validation measurements were carried out for each system, including measurements for a complete IMRT treatment. The reproducibility of dynamic delivery and the characteristics of the accelerator for low-monitor-unit (MU) deliveries were also assessed. An extensive quality assurance (QA) program was performed for each of the patients. Additionally, timing measurements were carried out to assess the practicalities of the technique. RESULTS: The planning objectives were met in most cases. Absolute doses for complete IMRT treatments were within 2%, on average, with dose distributions generally showing agreement within 3% or 3 mm. Beam modulation measurements made throughout each patient's treatment indicated that both delivery methods were reproducible. The dynamic plans required an average of 765 MU per beam, with a treatment delivery time of 14 min; corresponding results for step-and-shoot plans were 105 MU and 10 min. CONCLUSIONS: Two IMRT techniques for this group of patients have been successfully implemented in the clinic. The more complex dynamic treatments showed no advantages over the step-and-shoot approach. QA results have shown accurate and reproducible delivery for both techniques, giving increased confidence in the techniques and allowing a reduction in the QA program.

Humans↗
PubMed2005

Development of a dynamic strategy planning theory and system for sustainable river basin land use management.

Land use management is central to government planning for sustainable development. The main purpose of this study is to develop a novel strategy planning theory and system to assist responsible authorities in obtaining alternatives of sustainable top river basin land use management. The concepts and theory of system analysis, driving force-state-response (DSR) framework, and system dynamics are used to establish the DSR dynamic strategy planning procedure in this work. The integrated management of the land, water, and air resources of a river basin system is considered in the procedure. Two modified land use management procedures combined with the DSR dynamic strategy planning procedure are developed in this work. Based on the DSR dynamic strategy planning procedure, the sustainable river basin land use management DSR dynamic decision support system (SRBLUM-DSRD-DSS) is developed by using the Vensim, MS Excel, ArcView, and Visual Basic software. The concepts of object-orientation are used to develop the system dynamic optimization and simulation models of SRBLUM-DSRD-DSS. Based on the modified land use management procedures, SRBLUM-DSRD-DSS is used to assist decision makers in generating the land use plans of the Nankan river basin in Taoyuan County of Taiwan. Since the decisions of land, water and air resources management are still made at different agencies, the land use management system should be modified based on the innovational procedure to implement the management strategy developed in this work. The results show that the modified land use management procedures can be a guidance for the governments in modifying the systems and regulation of urban and regional plans in Taiwan.

Cities↗
PubMed2004

Dynamic acoustic radiation force acting on cylindrical shells: theory and simulations.

An object placed in an acoustic field is known to experience a force due to the transfer of momentum from the wave to the object itself. This force is known to be steady when the incident field is considered to be continuous with constant amplitude. One may define the dynamic (oscillatory) radiation force for a continuous wave-field whose intensity varies slowly with time. This paper extends the theory of the dynamic acoustic radiation force resulting from an amplitude-modulated progressive plane wave-field incident on solid cylinders to the case of solid cylindrical shells with particular emphasis on their thickness and contents of their hollow regions. A new factor corresponding to the dynamic radiation force is defined as Y(d) and stands for the dynamic radiation force per unit energy density and unit cross sectional surface. The results of numerical calculations are presented, indicating the ways in which the form of the dynamic radiation force function curves are affected by variations in the material mechanical parameters and by changes in the interior fluid inside the shell's hollow region. It was shown that the dynamic radiation force function Y(d) deviates from the static radiation force function for progressive waves Y(p) when the modulation frequency increases. These results indicate that the theory presented here is broader than the existing theory on cylinders.

Algorithms↗
PubMed2006

Test stimulus characteristics determine the perceived speed of the dynamic motion aftereffect.

Using a speed-matching task, we measured the speed tuning of the dynamic motion aftereffect (MAE). The results of our first experiment, in which we co-varied dot speed in the adaptation and test stimuli, revealed a speed tuning function. We sought to tease apart what contribution, if any, the test stimulus makes towards the observed speed tuning. This was examined by independently manipulating dot speed in the adaptation and test stimuli, and measuring the effect this had on the perceived speed of the dynamic MAE. The results revealed that the speed tuning of the dynamic MAE is determined, not by the speed of the adaptation stimulus, but by the local motion characteristics of the dynamic test stimulus. The role of the test stimulus in determining the perceived speed of the dynamic MAE was confirmed by showing that, if one uses a test stimulus containing two sources of local speed information, observers report seeing a transparent MAE; this is despite the fact that adaptation is induced using a single-speed stimulus. Thus while the adaptation stimulus necessarily determines perceived direction of the dynamic MAE, its perceived speed is determined by the test stimulus. This dissociation of speed and direction supports the notion that the processing of these two visual attributes may be partially independent.

Figural Aftereffect↗
PubMed2000

Demand dynamic cardiomyoplasty: mechanograms prove incomplete transformation of the rested latissimus dorsi.

BACKGROUND: In dynamic cardiomyoplasty, standard stimulation produces high fatigue resistance but also undesirable dynamic characteristics of the latissimus dorsi (LD). Based on results of intermittent stimulation in animals we introduced demand stimulation, a lighter regimen of LD activity-rest stimulation, and the mechanogram, a noninvasive method to determine the contractile characteristics of LD wrap. METHODS: Surgery and standard stimulation was according to the technique of Carpentier and Chachques, demand stimulation and LD wrap mechanogram were as we previously described. The LD contraction is synchronized to heart systole by mechanogram and echocardiography, and extent of transformation by tetanic fusion frequency analysis. A total of 22 patients were studied to date. Data for the 8 subjects who attained 6-month follow-up are reported. Four of them were lightly stimulated from the conditioning period, whereas 4 others were converted to light and then demand stimulation after years of standard stimulation. Patients were followed up with respect to survival, functional class, hospital admission rate, medication used, cardiopulmonary exercise testing, and LD wrap mechanography. RESULTS: Latissimus dorsi wrap slowness reverses by the activity-rest regimen, even after years of standard stimulation (Tetanic fusion frequency of 11 +/- 2 Hz after standard stimulation vs 30 +/- 3 Hz after demand regimen, p < 0.0001). After demand dynamic cardiomyoplasty there are no deaths. Quality of life is substantially improved with significant reduction of heart failure symptoms (New York Heart Association class: preoperative 3.0 +/- 0.0, post-demand dynamic cardiomyoplasty 1.5 +/- 0.2, p < 0.0001). In the subgroup of patients lightly stimulated from LD conditioning, exercise capacity tends to increase over preoperative values more than 2 years after operation (VO2 max: preoperative 12.3 +/- 0.7 vs 16.6 +/- 1.7 post-demand dynamic cardiomyoplasty, p = 0.05). CONCLUSIONS: Demand stimulation and mechanography of the LD wrap are safe procedures that could offer long-term benefits of dynamic cardiomyoplasty to patients with pharmacologically intractable heart failure.

Adult↗
PubMed1999

Dynamic cardiomyoplasty: at the crossroads.

BACKGROUND: Dynamic cardiomyoplasty remains a promising, but still unproven surgical treatment for patients with end-stage heart failure. Lack of a clear survival advantage and ongoing misunderstanding of its mechanism of action have hindered its acceptance as a treatment alternative for patients with end-stage heart failure. This review seeks to update current clinical results and practice of dynamic cardiomyoplasty and to present its likely mechanism of action. METHODS: The method involved a literature review. RESULTS: More than 600 patients have undergone dynamic cardioplasty since 1985. Improvement in average New York Heart Association class was noted in 80% to 85% of hospital survivors. Operative mortality has decreased from 31% in Phase I to less than 3% in the ongoing Phase III trial. Clinical work as well as recent animal work supports the hypothesis that through a combination of long-term elastic constraint and active dynamic assist, dynamic cardiomyoplasty decreases myocardial wall stress associated with the remodeling process of progressive heart failure. CONCLUSIONS: Though dynamic cardiomyoplasty can be shown to limit the remodeling process of heart failure in animal studies and some patients, its ultimate role in the treatment of heart failure will depend on the outcome of randomized, controlled studies.

Cardiomyoplasty↗
PubMed1999

Seating pressures with conventional and dynamic wheelchair cushions in tetraplegia.

OBJECTIVE: To compare pressure relief from a dynamic wheelchair cushion to a tilt-in-space wheelchair with conventional cushions. STUDY DESIGN: Repeated measures analysis. SETTING AND SUBJECTS: Spinal cord injury unit; 16 tilt-in-space wheelchair users with motor-complete tetraplegia. MAIN OUTCOME MEASURES: Interface pressure at ischial tuberosities. RESULTS: Mean ischial pressure with subjects seated upright on the dynamic cushion during the low ischial pressure phase was lower than tilted pressure on the gel cushion, but it was not significantly different from tilted pressure on the dry-flotation cushion (dynamic/upright, 71 mm Hg; gel/tilted, 86 mm Hg; dry-flotation/tilted, 74 mm Hg; p<.05 dynamic vs. gel). Mean ischial pressure with subjects upright on the dynamic cushion during the high ischial pressure phase was significantly greater than the gel/upright and dry-flotation/upright conditions (dynamic/upright, 157 mm Hg; gel/upright, 128 mm Hg; dry-flotation/upright, 111 mm Hg; p<.001). CONCLUSION: The dynamic cushion produces similar pressure relief over the ischial tuberosities during the low pressure phase to a tilt-in-space wheelchair and conventional cushions. The dynamic cushion may be an alternative to a tilt-in-space wheelchair for some individuals.

Adult↗
PubMed2006

Effect of endotracheal suction on lung dynamics in mechanically-ventilated paediatric patients.

Endotracheal suctioning is performed regularly in ventilated infants and children to remove obstructive secretions. The effect of suctioning on respiratory mechanics is not known. This study aimed to determine the immediate effect of endotracheal suctioning on dynamic lung compliance, tidal volume, and airway resistance in mechanically-ventilated paediatric patients by means of a prospective observational clinical study. Lung mechanics were recorded for five minutes before and five minutes after a standardised suctioning procedure in 78 patients intubated with endotracheal tubes < or = 4.0 mm internal diameter. Twenty-four patients with endotracheal tube leaks > or = 20% were excluded from analysis. There was a significant overall decrease in dynamic compliance (p < 0.001) and mechanical expired tidal volume (p = 0.03) following suctioning with no change in the percentage endotracheal tube leak (p = 0.41). The change in dynamic compliance was directly related to both endotracheal tube and catheter sizes. There was no significant change in expiratory or inspiratory airway resistance following suctioning (p > 0.05). Although the majority of patients (68.5%) experienced a drop in dynamic compliance following suctioning, dynamic compliance increased in 31.5% of patients after the procedure. This study demonstrates that endotracheal suctioning frequently causes an immediate drop in dynamic compliance and expired tidal volume in ventilated children with variable lung pathology, intubated with small endotracheal tubes, probably indicating loss of lung volume caused by the suctioning procedure. There is no evidence that suctioning reduces airway resistance.

Airway Resistance↗
PubMed2000

Membrane dynamics as seen by fourier transform infrared spectroscopy in a cyanobacterium, Synechocystis PCC 6803. The effects of lipid unsaturation and the protein-to-lipid ratio.

The roles of lipid unsaturation and lipid-protein interactions in maintaining the physiologically required membrane dynamics were investigated in a cyanobacterium strain, Synechocystis PCC 6803. The specific effects of lipid unsaturation on the membrane structure were addressed by the use of desaturase-deficient (desA(-)/desD(-)) mutant cells (which contain only oleic acid as unsaturated fatty acid species) of Synechocystis PCC 6803. The dynamic properties of the membranes were determined from the temperature dependence of the symmetric CH(2) stretching vibration frequency, which is indicative of the lipid fatty acyl chain disorder. It was found that a similar membrane dynamics is maintained at any growth temperature, in both the wild-type and the mutant cell membranes, with the exception of mutant cells grown at the lower physiological temperature limit. It seems that in the physiological temperature range the desaturase system of the cells can modulate the level of lipid desaturation sufficiently to maintain similar membrane dynamics. Below the range of normal growth temperatures, however, the extent of lipid disorder was always higher in the thylakoid than in the cytoplasmic membranes prepared from the same cells. This difference was attributed to the considerable difference in protein-to-lipid ratio in the two kinds of membranes, as determined from the ratio of the intensities of the protein amide I band and the lipid ester C&z.dbnd6;O vibration. The contributions to the membrane dynamics of an ab ovo present 'structural' lipid disorder due to the protein-lipid interactions and of a thermally induced 'dynamic' lipid disorder could be distinguished.

Cell Membrane↗
PubMed2002

Dynamic flux balance analysis of diauxic growth in Escherichia coli.

Flux Balance Analysis (FBA) has been used in the past to analyze microbial metabolic networks. Typically, FBA is used to study the metabolic flux at a particular steady state of the system. However, there are many situations where the reprogramming of the metabolic network is important. Therefore, the dynamics of these metabolic networks have to be studied. In this paper, we have extended FBA to account for dynamics and present two different formulations for dynamic FBA. These two approaches were used in the analysis of diauxic growth in Escherichia coli. Dynamic FBA was used to simulate the batch growth of E. coli on glucose, and the predictions were found to qualitatively match experimental data. The dynamic FBA formalism was also used to study the sensitivity to the objective function. It was found that an instantaneous objective function resulted in better predictions than a terminal-type objective function. The constraints that govern the growth at different phases in the batch culture were also identified. Therefore, dynamic FBA provides a framework for analyzing the transience of metabolism due to metabolic reprogramming and for obtaining insights for the design of metabolic networks.

Cell Division↗
PubMed2003

Molecular dynamics decomposition of temperature-dependent elastic neutron scattering by a protein solution.

Molecular dynamics simulations are performed of bovine pancreatic trypsin inhibitor in a cryosolution over a range of temperatures from 80 to 300 K and the origins identified of elastic dynamic neutron scattering from the solution. The elastic scattering and mean-square displacement calculated from the molecular dynamics trajectories are in reasonable agreement with experiments on a larger protein in the same solvent. The solvent and protein contributions to the scattering from the simulation model are determined. At lower temperatures (< approximately 200 K) or on shorter timescales ( approximately 10 ps) the scattering contributions are proportional to the isotopic nuclear scattering cross-sections of each component. However, for T > 200 K marked deviations from these cross-sections are seen due to differences in the dynamics of the components of the solution. Rapid activation of solvent diffusion leads to the variation with temperature of the total elastic intensity being determined largely by that of the solvent. At higher temperatures (>240 K) and longer times ( approximately 100 ps) the protein makes the only significant contribution to the scattering, the solvent scattering having moved out of the accessible time-space window. Decomposition of the protein mean-square displacement shows that the observed dynamical transition in the solution at 200-220 K involves activation of both internal motions and external whole-molecule rotational and translational diffusion. The proportion that the external dynamics contributes to the protein mean-square displacement increases to approximately 30 and 60% at 300 K on the 10- and 100-ps timescales, respectively.

Aprotinin↗
PubMed1993

Molecular dynamics simulations of heme reorientational motions in myoglobin.

Molecular dynamics simulations of 2-ns duration were performed on carbonmonoxymyoglobin and deoxymyoglobin in vacuo to study the reorientational dynamics of the heme group. The heme in both simulations undergoes reorientations of approximately 5 degrees amplitude on a subpicosecond time scale, which produce a rapid initial decay in the reorientational correlation function to about 0.99. The heme also experiences infrequent changes in average orientation of approximately 10 degrees amplitude, which lead to a larger slow decay of the reorientational correlation function over a period of hundreds of picoseconds. The simulations have not converged with respect to these infrequent transitions. However, an estimate of the order parameter for rapid internal motions of the heme from those orientations which are sampled by the simulations suggests that the subnanosecond orientational dynamics of the heme accounts for at least 30% of the unresolved initial anisotropy decay observed in the nanosecond time-resolved optical absorption experiments on myoglobin reported by Ansari et al. in a companion paper (Ansari, A., C.M. Jones, E.R. Henry, J. Hofrichter, and W.A. Eaton. 1992. Biophys. J. 64:852-868.). A more complete sampling of the accessible heme orientations would most likely increase this fraction further. The simulation of the liganded molecule also suggests that the conformational dynamics of the CO ligand may contribute significantly to discrepancies between the ligand conformation as probed by x-ray diffraction and by infrared-optical photoselection experiments. The protein back-bone explores multiple conformations during the simulations, with the largest structural changes appearing in the E and F helices, which are in contact with the heme. The variations in the heme orientation correlate with the conformational dynamics of the protein on a time scale of hundreds of picoseconds, suggesting that the heme orientation may provide a useful probe of dynamical processes in the protein.

Animals↗
PubMed1996

The consistency of large concerted motions in proteins in molecular dynamics simulations.

A detailed investigation is presented into the effect of limited sampling time and small changes in the force field on molecular dynamics simulations of a protein. Thirteen independent simulations of the B1 IgG-binding domain of streptococcal protein G were performed, with small changes in the simulation parameters in each simulation. Parameters studied included temperature, bond constraints, cut-off radius for electrostatic interactions, and initial placement of hydrogen atoms. The essential dynamics technique was used to reveal dynamic differences between the simulations. Similar essential dynamics properties were found for all simulations, indicating that the large concerted motions found in the simulations are not particularly sensitive to small changes in the force field. A thorough investigation into the stability of the essential dynamics properties as derived from a molecular dynamics simulation of a few hundred picoseconds is provided. Although the definition of the essential modes of motion has not fully converged in these short simulations, the subspace in which these modes are confined is found to be reproducible.

Antigens, Bacterial↗
PubMed1996

Water in channel-like cavities: structure and dynamics.

Ion channels contain narrow columns of water molecules. It is of interest to compare the structure and dynamics of such intrapore water with those of the bulk solvent. Molecular dynamics simulations of modified TIP3P water molecules confined within channel-like cavities have been performed and the orientation and dynamics of the water molecules analyzed. Channels were modeled as cylindrical cavities with lengths ranging from 15 to 60 A and radii from 3 to 12 A. At the end of the molecular dynamics simulations water molecules were observed to be ordered into approximately concentric cylindrical shells. The waters of the outermost shell were oriented such that their dipoles were on average perpendicular to the normal of the wall of the cavity. Water dynamics were analyzed in terms of self-diffusion coefficients and rotational reorientation rates. For cavities of radii 3 and 6 A, water mobility was reduced relative to that of simulated bulk water. For 9- and 12-A radii confined water molecules exhibited mobilities comparable with that of the bulk solvent. If water molecules were confined within an hourglass-shaped cavity (with a central radius of 3 A increasing to 12 A at either end) a gradient of water mobility was observed along the cavity axis. Thus, water within simple models of transbilayer channels exhibits perturbations of structure and dynamics relative to bulk water. In particular the reduction of rotational reorientation rate is expected to alter the local dielectric constant within a transbilayer pore.

Biophysical Phenomena↗
PubMed1997

Dynamic strength of molecular adhesion bonds.

In biology, molecular linkages at, within, and beneath cell interfaces arise mainly from weak noncovalent interactions. These bonds will fail under any level of pulling force if held for sufficient time. Thus, when tested with ultrasensitive force probes, we expect cohesive material strength and strength of adhesion at interfaces to be time- and loading rate-dependent properties. To examine what can be learned from measurements of bond strength, we have extended Kramers' theory for reaction kinetics in liquids to bond dissociation under force and tested the predictions by smart Monte Carlo (Brownian dynamics) simulations of bond rupture. By definition, bond strength is the force that produces the most frequent failure in repeated tests of breakage, i.e., the peak in the distribution of rupture forces. As verified by the simulations, theory shows that bond strength progresses through three dynamic regimes of loading rate. First, bond strength emerges at a critical rate of loading (> or = 0) at which spontaneous dissociation is just frequent enough to keep the distribution peak at zero force. In the slow-loading regime immediately above the critical rate, strength grows as a weak power of loading rate and reflects initial coupling of force to the bonding potential. At higher rates, there is crossover to a fast regime in which strength continues to increase as the logarithm of the loading rate over many decades independent of the type of attraction. Finally, at ultrafast loading rates approaching the domain of molecular dynamics simulations, the bonding potential is quickly overwhelmed by the rapidly increasing force, so that only naked frictional drag on the structure remains to retard separation. Hence, to expose the energy landscape that governs bond strength, molecular adhesion forces must be examined over an enormous span of time scales. However, a significant gap exists between the time domain of force measurements in the laboratory and the extremely fast scale of molecular motions. Using results from a simulation of biotin-avidin bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K. Schulten. 1997. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J., this issue), we describe how Brownian dynamics can help bridge the gap between molecular dynamics and probe tests.

Avidin↗
PubMed1999

Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia.

Ventricular fibrillation (VF), the major cause of sudden cardiac death, is typically preceded by ventricular tachycardia (VT), but the mechanisms underlying the transition from VT to VF are poorly understood. Intracellular Ca(2+) overload occurs during rapid heart rates typical of VT and is also known to promote arrhythmias. We therefore studied the role of intracellular Ca(2+) dynamics in the transition from VT to VF, using a combined experimental and mathematical modeling approach. Our results show that 1) rapid pacing of rabbit ventricular myocytes at 35 degrees C led to increased intracellular Ca(2+) levels and complex patterns of action potential (AP) configuration and the intracellular Ca(2+) transients; 2) the complex patterns of the Ca(2+) transient arose directly from the dynamics of intracellular Ca(2+) cycling, and were not merely passive responses to beat-to-beat alterations in AP; 3) the complex Ca(2+) dynamics were simulated in a modified version of the Luo-Rudy (LR) ventricular action potential with improved intracellular Ca(2+) dynamics, and showed good agreement with the experimental findings in isolated myocytes; and 4) when incorporated into simulated two-dimensional cardiac tissue, this action potential model produced a form of spiral wave breakup from VT to a VF-like state in which intracellular Ca(2+) dynamics played a key role through its influence on Ca(2+)-sensitive membrane currents such as I(Ca), I(NaCa), and I(ns(Ca)). To the extent that spiral wave breakup is useful as a model for the transition from VT to VF, these findings suggest that intracellular Ca(2+) dynamics may play an important role in the destabilization of VT and its degeneration into VF.

Action Potentials↗
PubMed1999

Molecular dynamics simulations of solvated yeast tRNA(Asp).

Transfer RNA molecules are involved in a variety of biological processes, implying complex recognition events with proteins and other RNAs. From a structural point of view, tRNAs constitute a reference system for studying RNA folding and architecture. A deeper understanding of their structural and functional properties will derive from our ability to model accurately their dynamical behavior. We present the first dynamical model of a fully neutralized and solvated tRNA molecule over a 500-ps time scale. Starting from the crystallographic structure of yeast tRNA(Asp), the 75-nucleotide molecule was modeled with 8055 water molecules and 74 NH4+ counterions, using the AMBER4.1 program and the particle mesh Ewald (PME) method for the treatment of long-range electrostatic interactions. The calculations led to a dynamically stable model of the tRNA molecule. During the simulation, all secondary and tertiary base pairs are maintained while a certain lability of base triples in the tRNA core is observed. This lability was interpreted as resulting from intrinsic factors associated with the "weaker" hydrogen bonding patterns seen in these base triples and from an altered ionic environment of the tRNA molecule. Calculated thermal factors are used to compare the dynamics of the tRNA in solution and in the crystal. The present molecular dynamics simulation of a complex and highly charged nucleic acid molecule attests to the fact that simulation methods are now able to investigate not only the dynamics of proteins, but also that of large RNA molecules. Thus they also provide a basis for further investigations on the structural and functional effects of chemical and posttranscriptionally modified nucleotides as well as on ionic environmental effects.

Base Pairing↗