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At least 163 records · Page 9Linked to original sources
PubMed1991

Predicting the three-dimensional folding of transfer RNA with a computer modeling protocol.

We have developed a computer modeling protocol that can be used to predict the three-dimensional folding of a ribonucleic acid on the basis of limited amounts of secondary and tertiary data. This protocol extends the use of distance geometry beyond the domain of NMR data in which it is usually applied. The use of this algorithm to fold the molecule eliminates operator subjectivity and reproducibly predicts the overall dimensions and shape of the transfer RNA molecule. By use of a replacement pseudoatom set based on helical substructures, a series of transfer RNA foldings have been completed that utilize only the primary structure, the phylogenetically deduced secondary structure, and five long-range interactions that were determined without reference to the crystal structure. In a control set of foldings, all the interactions suspected to exist in 1969 have been included. In all cases, the modeling process consistently predicts the global arrangement of the helical domains and to a lesser extent the general path of the backbone of transfer RNA.

Computer Simulation↗
PubMedDate not supplied

[Stochastic computer model of cellular microtubule dynamics].

A computer model of the system of microtubules has been developed to study the mechanisms of action of various factors on this system. The model describes the process of polymerization/depolymerization of microtubules as a set of chemical reactions with certain rate constants using a stochastic approach. Microtubules are visualized in the program field, which makes the model visual. The program imitates the dynamics and structure of the system of cellular microtubules with great, reliability. The parameters generated by the model correlate with the corresponding parameters of microtubules in living cells. We are going to develop this approach to modeling microtubules and similar structures to bring them into a better accord with living systems and to study the influence of various factors on these systems.

Computer Simulation↗
PubMed1993

A computer model of the convulsive membrane.

A computer model of the convulsive membrane was built up by combining the H-H equations of normal ionic currents with a pathological current flowing through calcium channels and carrying sodium ions. Thus any form of paroxysmal depolarization shift could be simulated, by varying two rate constants and potassium conductance. The simulated PDSs are initiated by a minimal conductance pulse and terminate spontaneously according to the inherent rules of the model system. The program is written in Turbo-Pascal language and can be run on any PC.

Calcium Channels↗
PubMed1991

Identification of antibody epitopes within the CB-11 peptide of type II collagen. II. Computer modelling studies of peptides and the interpretation of epitope scanning results.

Computer modelling techniques were used to investigate the structure of 8-mers from the CB-11 peptide of bovine type II collagen which were recognised by sera from rats which had previously been injected with bovine type II collage. It was discovered that all the hydrophobic peptides recognised by the rat sera were predicted to have collagenous-like secondary structures. The primary structure of the 8-mers which were recognised was also compared against the sequences in the OWL protein sequence database. The combined results of the computer modelling and sequence analysis suggested that the sequence Gly-Pro-Gly-Phe-Pro is a minimal B cell epitope of the CB-11 fragment of bovine type II collagen.

Amino Acid Sequence↗
PubMed1981

Predictive validity of a computer model of body temperature during exercise.

The predictive validity of a computer model of human temperature regulation is tested by comparison with experimental data. Three male subjects were exercised at five different rates (B.M.R., 100 W, 150 W, 200 W, and 250 W) on a cycle ergometer in a controlled-environmental facility. Thermal conditions ranged from 13 degrees to 29 degrees C on the Effective Temperature (E.T.) scale. Two core (rectal and tympanic) and four skin temperature sites (2 torso, 1 leg, and 1 arm) were monitored. Experimental figures for core temperature (TC) and mean body temperature (MBT), evolved from the six monitored sites, were compared with matched simulation data from the computer model. A high negative correlation (r = -0.87) was found for increasing "effective temperature" and mean absolute difference (d) between experimental and simulation data for mean body temperatures. The model has increasing predictive validity as higher heat stress is encountered (E.T. greater than 25 degrees C, d MBT less than 0.3 degrees C), which decreases (E.T. less than 16 degrees C, d MBT greater than 0.8 degrees C) in reduced environmental temperatures.

Body Temperature Regulation↗
PubMedDate not supplied

[Computer modeling of the effective search].

A computer model of vector-Brownian processes is proposed, which can be applied to some biophysical problems including the problem of search efficiency. The results obtained suggest that the changes in the ratio of two components (the vector and the Brownian ones) in any process essentially improve the efficiency of search.

Animals↗
PubMed2000

Cost analysis of the treatment of vesicoureteral reflux: a computer model.

PURPOSE: Surgical intervention for vesicoureteral reflux is generally limited to children who have recurrent infection despite adequate antimicrobial prophylaxis or in whom compliance with followup cannot be ensured. In addition, surgical therapy is considered in children with persistent reflux after a reasonable period of surveillance. We used a model based on the management of a theoretical population of girls with various grades of reflux and followed the costs incurred during a 5-year management period. MATERIALS AND METHODS: The literature on vesicoureteral reflux was used to create a set of assumptions regarding epidemiology, likelihood of resolution, need for operative intervention, risk of infection and appropriate regimen for nonoperative surveillance. These parameters were evaluated in infants and children as noted in the literature. A 5-year management period was considered. Patients in whom reflux did not resolve with medical management at the end of 5 years were assumed to have undergone surgical correction. Costs were calculated based on the amounts billed, managed care reimbursement and Medicaid reimbursement in Maryland. The costs of up front surgical management were calculated and compared to those of 5 years of standard management. All costs were discounted at a rate of 10%. RESULTS: Calculated costs of standard management were lower for lower grades than those for higher grades of reflux. The costs of surgical management were lower than those of standard management for higher reflux grades using nondiscounted costs. However, when costs were discounted to present value, the costs of standard management were significantly lower than those of up-front surgery for all scenarios studied. CONCLUSIONS: The cost of vesicoureteral reflux is considerable when whole patient groups are considered. Using cost as the only parameter the standard management of reflux is less costly than up-front surgery. In the individual surgical intervention usually is predicated by patient and family factors which were not considered in this model. This computer based construct allows data from different institutions to be analyzed to project costs of the management of reflux.

Child↗
PubMed2003

Computational modeling of the EGF-receptor system: a paradigm for systems biology.

Computational models have rarely been used as tools by biologists but, when models provide experimentally testable predictions, they can be extremely useful. The epidermal growth factor receptor (EGFR) is probably the best-understood receptor system, and computational models have played a significant part in its elucidation. For many years, models have been used to analyze EGFR dynamics and to interpret mutational studies, and are now being used to understand processes including signal transduction, autocrine loops and developmental patterning. The success of EGFR modeling can be a guide to combining models and experiments productively to understand complex biological processes as integrated systems.

Animals↗
PubMed1993

An augmented computer model of motor unit reorganization in neurogenic diseases of skeletal muscle.

A computer model of denervation and complete reinnervation in skeletal muscle was originally developed for the purpose of furthering an understanding of the underlying mechanisms of motor unit reorganization in neurogenic diseases. We now describe its successor, a computer model for investigating different rates of denervation and reinnervation, as well as incomplete reinnervation. The new model introduces the concept of permanent denervation and features enhanced interactive control over the distribution of motor unit centers and additional measures of dispersion and co-dispersion of muscle fibers. The use of this model for investigating pathophysiologically significant issues in denervating diseases is illustrated with five different sets of parameters. These simulate some of the processes that may be operational in chronic spinal muscular atrophy, amyotrophic lateral sclerosis, and progressive postpolio muscular dystrophy. The enhanced model will allow in-depth analysis of the influence of hypothesized pathophysiological processes on clinical, electrophysiological and pathological outcomes in human disease.

Computer Simulation↗
PubMed1993

The fractional volume available to prolate spheroids in a network of randomly oriented fibers obtained by computer modeling: correlation with the Ogston equation.

Computer modeling was used to measure the fractional volumes available to prolate spheroid objects in a random, inert network of fibers. The data fit the Ogston equation exactly when the object was a sphere (axial ratio = 1). When the axial ratio was increased from 1 to 9, the Ogston equation was still obeyed if the fiber concentration is multiplied by a factor, A, which increases linearly in proportion to the axial ratio. The factor A allows one to adjust the retardation coefficient derived from gel electrophoresis, KR, for spherical objects to that of prolate spheroids with axial ratios from 1 to 9. Potentially, the same adjustment of KR is possible for objects of other shapes.

Algorithms↗
PubMed1990

[Analysis of dynamic changes in glycosylated blood proteins using a computer model].

UNLABELLED: The authors elaborated a computer model of albumin glycosylation based on the irreversible glycosylation reaction with first order kinetics. The dynamics of changes of glycosylated albumin in relation to the glycaemic profile was confirmed with an older model of haemoglobin glycosylation. By means of regression analysis parameters of the model in three groups of patients were calculated. CONCLUSION: 1. Stratification of the red cell pool is the reason why there is a smaller clinical difference between glycosylated protein and haemoglobin than corresponds to their half-times. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated ones. 3. Higher levels of glycosylated proteins sometimes do not correspond to model calculations are probably due to other factors.

Computer Simulation↗
PubMed1983

Predictions of a network thermodynamics computer model relating to the mechanism of methotrexate rescue by 5-formyltetrahydrofolate and to the importance of inhibition of thymidylate synthase by methotrexate-polyglutamates.

Computer modeling has been a valuable tool for clarifying the mechanism of action of antifolates. Some consequences of folyl and antifolyl polyglutamate synthesis can be addressed by adaptation of a network thermodynamic computer model of methotrexate action. Reversal or prevention of methotrexate cytotoxicity by 5-formyltetrahydrofolate has widely been assumed to occur through the delivery of reduced folate in substrate amounts for thymidylate synthesis, by-passing the effects of methotrexate at dihydrofolate reductase. This mechanism is inconsistent with experimental data which shows that "rescue" is a competitive phenomenon and that the transport process is incapable of delivering reduced folate at an adequate rate. Computer modeling studies are presented which predict that expansion of the total folate pool as folylpolyglutamates with "rescue" would reduce the inhibitory effect of MTX on thymidylate synthesis. Dihydrofolate polyglutamates could then accumulate to the high level needed to displace methotrexate from the small fraction of sites on dihydrofolate reductase that are sufficient to sustain tetrahydrofolate synthesis. Experimental studies with Ehrlich ascites tumor cells support this prediction. It is likely that a critical step in the protection of normal host tissues in high dose-rescue treatment regimens is the conversion of exogenously supplied 5-formyltetrahydrofolate to polyglutamyl derivatives and accumulation of total intracellular folate to higher than normal levels. Other computer simulations are presented which examine the potential significance of direct inhibition of thymidylate synthase by polyglutamyl forms of methotrexate. The model predicts that in cells with biochemical properties similar to methotrexate sensitive L1210 cells, inhibition of dihydrofolate reductase would still be the predominant site of action unless the thymidylate synthase Ki for a methotrexate polyglutamate is below about 0.1 microM. However, in methotrexate-resistant cells with elevated dihydrofolate reductase but normal membrane transport and polyglutamylation, thymidylate synthase may be the more important target enzyme.

Computers↗
PubMed1992

Computer modeling of gibberellin-DNA binding.

Computer modeling and molecular mechanics performed on the intercalation complexes of selected gibberellins or biosynthetic precursors with DNA dinucleotides revealed that under appropriate conditions the ligands insert (intercalate) between the base-paired double-stranded dinucleotide, 5'-dTdA-3'. Stabilization of the double-stranded dinucleotide after docking of a gibberellin between base pairs is inferred by the sum negative energy of hydrogen bonding and van der Waals contacts and the entropic changes which accompany the formation of each ligand-dinucleotide complex. In addition, the interactions of the gibberellins and dinucleotides, with the gibberellic acid-dinucleotide complex serving as the prototype, show optimum geometry and stereochemical hydrogen bonding recognition which are dependent upon the complementary chirality and stereochemistry of the individual components. Whether or not the gibberellins directly influence the uncoiling of DNA or gene expression at the transcriptional level via an intercalation mechanism is a matter of conjecture, albeit one that warrants intensive investigation.

Computer Simulation↗
PubMed1999

The dynamics of vortex-like reentry wave filaments in three-dimensional computer models.

Recent studies using computer simulation and biological studies in 2-dimensional excitable media have suggested that spiral wave reentrant activation and its core dynamics are important elements in the mechanism of functional reentrant tachyarrhythmias, such as atrial and ventricular fibrillation. However, vortex-like reentry has been observed in homogeneous 3-dimensional excitable media, and the dynamics of the related "filaments," which have 3-dimensionally connected "cores" in 2 dimensions, have not been clarified. In order to determine whether the filaments of vortex-like reentry waves can be observed in 3-dimensional media using a mathematical ionic current heart model and whether the abnormal ionic currents in myocardium affect the complexity of the filaments, we studied the qualitative features of vortex-like reentry dynamics using mathematical models in computer simulations. We employed the Luo-Rudy Phase I and the FitzHugh-Nagumo models for our heart media, which were cubic and ventricular shaped, and consisted of 8,000,000 and 5,636,654 myocardial units, respectively. Functional reentry, in the form of vortex waves, was induced in the media by the S1-S2 method. The vortex-like reentry waves and their filaments were displayed by computer graphics. Computations were performed on an NEC SX-4 supercomputer (NEC, Tokyo, Japan) using programs written in C language. Computer simulation studies have shown that the filament dynamics of vortex-like reentry in the original Luo-Rudy model is considerably more complex than that in the FitzHugh-Nagumo model. However, when we mathematically modified the L-type calcium current and shortened the action potential duration, just as occurs with sustained rapid ventricular pacing, the dynamics of the vortex-like reentrant wave fronts and the filaments were similar in both models. Our results suggested that the original character of myocardium causes drastic changes in filament shape and location, resulting in intricate functional reentrant waves, and that if the L-type calcium current is depressed, the complexity of the dynamics of the filaments are decreased to some degree.

Calcium↗
PubMed2003

Shape of the left ventricle and its computer modelling.

A simple computer program was made to draw different left ventricle shapes in order to support the theory of elongation and to get a visual presentation of the shape of the left ventricle. Experimental data, obtained from echocardiography and Simpson's rule, were used for this program. The results yielded different shapes under different physiological circumstances, indicating the sensitivity of the method. It was concluded that these figures (shapes) support the use of elongation as a shape index.

Computer Simulation↗
PubMed1990

Analysis of glycosylated serum protein changes using a computer model.

UNLABELLED: The authors devised a computer model of albumin glycosylation based on irreversible glycosylation reaction of first-order kinetics. The dynamism of glycosylated albumin changes in relation to glycaemic profiles was compared with an earlier model of haemoglobin glycosylation. A non-linear regression analysis was employed to calculate the parameters of the model in three groups of patients. CONCLUSIONS: 1. Erythrocyte pool stratification accounts for the smaller clinical difference between glycosylated protein and haemoglobin than would correspond to their respective half-life values. 2. Glycosylated proteins are probably eliminated more rapidly than non-glycosylated proteins. 3. Higher levels of glycosylated proteins are occasionally at variance with model calculations, a fact which is probably due to other factors.

Computer Simulation↗