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At least 181 records · Page 10Linked to original sources
PubMed2006

A computational approach to botanical drug design by modeling quantitative composition-activity relationship.

Herbal medicine has been successfully applied in clinical therapeutics throughout the world. Following the concept of quantitative composition-activity relationship, the presented study proposes a computational strategy to predict bioactivity of herbal medicine and design new botanical drug. As a case, the quantitative relationship between chemical composition and decreasing cholesterol effect of Qi-Xue-Bing-Zhi-Fang, a widely used herbal medicine in China, was investigated. Quantitative composition-activity relationship models generated by multiple linear regression, artificial neural networks, and support vector regression exhibited different capabilities of predictive accuracy. Moreover, the proportion of two active components of Qi-Xue-Bing-Zhi-Fang was optimized based on the quantitative composition-activity relationship model to obtain new formulation. Validation experiments showed that the optimized herbal medicine has greater activity. The results indicate that the presented method is an efficient approach to botanical drug design.

Algorithms↗
PubMed2004

Development of a computational approach to predict blood-brain barrier permeability.

The objectives of this study were to generate a data set of blood-brain barrier (BBB) permeability values for drug-like compounds and to develop a computational model to predict BBB permeability from structure. The BBB permeability, expressed as permeability-surface area product (PS, quantified as logPS), was determined for 28 structurally diverse drug-like compounds using the in situ rat brain perfusion technique. A linear model containing three descriptors, logD, van der Waals surface area of basic atoms, and polar surface area, was developed based on 23 compounds in our data set, where the penetration across the BBB was assumed to occur primarily by passive diffusion. The correlation coefficient (R(2)) and standard deviation (S.D.) of the model-predicted logPS against the observed are 0.74 and 0.50, respectively. If an outlier was removed from the training data set, the R(2) and S.D. were 0.80 and 0.44, respectively. This new model was tested in two literature data sets, resulting in an R(2) of 0.77 to 0.94 and a S.D. of 0.38 to 0.51. For comparison, four literature models, logP, logD, log(D. MW(-0.5)), and linear free energy relationship, were tested using the set of 23 compounds primarily crossing the BBB by passive diffusion, resulting in an R(2) of 0.33 to 0.61 and a S.D. of 0.59 to 0.76. In summary, we have generated the largest PS data set and developed a robust three-descriptor model that can quantitatively predict BBB permeability. This model may be used in a drug discovery setting to predict the BBB permeability of new chemical entities.

Algorithms↗
PubMed2003

Computational approaches to motor learning by imitation.

Movement imitation requires a complex set of mechanisms that map an observed movement of a teacher onto one's own movement apparatus. Relevant problems include movement recognition, pose estimation, pose tracking, body correspondence, coordinate transformation from external to egocentric space, matching of observed against previously learned movement, resolution of redundant degrees-of-freedom that are unconstrained by the observation, suitable movement representations for imitation, modularization of motor control, etc. All of these topics by themselves are active research problems in computational and neurobiological sciences, such that their combination into a complete imitation system remains a daunting undertaking-indeed, one could argue that we need to understand the complete perception-action loop. As a strategy to untangle the complexity of imitation, this paper will examine imitation purely from a computational point of view, i.e. we will review statistical and mathematical approaches that have been suggested for tackling parts of the imitation problem, and discuss their merits, disadvantages and underlying principles. Given the focus on action recognition of other contributions in this special issue, this paper will primarily emphasize the motor side of imitation, assuming that a perceptual system has already identified important features of a demonstrated movement and created their corresponding spatial information. Based on the formalization of motor control in terms of control policies and their associated performance criteria, useful taxonomies of imitation learning can be generated that clarify different approaches and future research directions.

Humans↗
PubMed2006

Experimental and computational approach for evaluating the mechanical characteristics of dental composite resins with various filler sizes.

This study aimed to investigate the influence of particle size of fillers on flexural properties of dental composite resins by laboratory testing with computational analysis validation. Four kinds of silica fillers with mean particle sizes of 3.3, 4.3, 7.9, and 15.5 microm were used. Filler content was kept constant at 70 mass% (or 53.8 vol.%). The three-point bending test was performed with a constant loading speed of 1.0mm/min, and a span length of 20mm using an Instron machine, in order to measure flexural strength and modulus of composite resins with various particle sizes. Test specimens were 2-mm wide, 2-mm thick, and 25-mm long rectangular bars. Furthermore, a numerical simulation using three-dimensional finite element (FE) analysis was performed to investigate stress distribution in composite resins under loading. As a result, flexural strength decreased with increasing particle size of the filler of the composite resins (p<0.05). On the other hand, there was no significant difference in Young's modulus among composite resins with various filler sizes (p>0.05). Moreover, FE analysis indicated that stress concentration increased with increasing particle size in agreement with experimental results of flexural strength. In conclusion, within the limitations of this investigation, we confirmed that flexural strength of composite resins decreased with increasing filler particle size. In addition, FE analysis was effective for evaluating stress distributions of dental composite resins with various filler sizes.

Acrylic Resins↗
PubMed1969

Steady states of general multi-enzyme networks and their associated properties. Computational approaches.

This paper discusses the theoretical basis for the determination of the steady-state characteristics of a multi-enzyme network, given initial values for the enzyme and metabolite concentrations, and rate equations for each enzyme. The computation depends only to a small extent on integrating the rate equations, mainly on adjustment of the matrix of fluxes through each component of the system, until they are equal to each other within a prescribed tolerance limit.The program has been devised to be as flexible as possible to permit the user to investigate the effects of changing the concentration or kinetic properties of an individual enzyme. Alternatively, the concentrations of enzymes required to maintain a given flux may be computed. The program will deal with a network of up to about 30 enzymes.

Journal Article↗
PubMed2004

A computational approach to the synthesis of dirithromycin.

Dirithromycin is a macrolide antibiotic derived from erythromycin A. Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the condensation mechanism has been analyzed computationally by the AM1 method in the gas phase. First, the formation of the Schiff bases of dirithromycin and epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and epidirithromycin were considered. Finally, the epimerization of the Schiff base of epidirithromycin to the Schiff base of dirithromycin was investigated. Our results show that, even though carbinolamine forms faster for epidirithromycin than the corresponding structure for dirithromycin, dirithromycin is the major product of the synthesis.

Computational Biology↗
PubMed2002

The Hydrogen-Bond: computational approaches and applications to drug design.

This mini-review begins with a presentation of the hydrogen-bond in the context of other intermolecular recognition forces of significance in molecular biology and molecular pharmacology. This is followed by a survey of the various computational methods available to calculate the hydrogen-bonding capacity of compounds. Such methods use quantum mechanics, molecular mechanics, or algorithms based on experimental fragmental values. A recent and promising advance in the computation of H-bonding capacity is the development of specific molecular interaction fields (MIFs) known as molecular hydrogen-bonding potentials (MHBPs). Their interest in relating molecular properties to pharmacokinetic behaviour is highlighted with two examples, namely oral drug absorption and blood-brain barrier permeation.

Computational Biology↗
PubMed2004

Evaluation of DNA intercalation potential of pharmaceuticals and other chemicals by cell-based and three-dimensional computational approaches.

To what extent noncovalent chemical-DNA interactions, in particular weak nonbonded DNA intercalation, contribute to genotoxic responses in mammalian cells has not been fully elucidated. Moreover, with the exception of predominantly flat, multiple-fused-ring structures, our ability to predict intercalation ability of novel compounds is nearly completely lacking. Computational programs such as DEREK and MCASE recognize primarily those molecules that can form irreversible covalent adducts with DNA since their learning sets, for the most part, have not been populated by compounds for which a relationship between noncovalent interaction and genotoxicity exists. We describe here a novel three-dimensional (3D) computational DNA-docking model for prediction of DNA intercalative activity of molecules with both classical and nonclassical intercalating structures. The 3D docking results show a remarkable concordance with results obtained from testing these molecules directly in the Chinese hamster V79 cell-based bleomycin amplification system suggesting that either or both of these approaches may have utility in defining noncovalent chemical-DNA interactions. The ability to predict and/or demonstrate cellular DNA intercalation of novel molecules may well provide fresh insights into the nature and mechanistic basis of structurally unexpected genotoxicity observed during safety testing.

Animals↗
PubMed2004

Computational approaches for modeling regulatory cellular networks.

Cellular components interact with each other to form networks that process information and evoke biological responses. A deep understanding of the behavior of these networks requires the development and analysis of mathematical models. In this article, different types of mathematical representations for modeling signaling networks are described, and the advantages and disadvantages of each type are discussed. Two experimentally well-studied signaling networks are then used as examples to illustrate the insight that could be gained through modeling. Finally, the modeling approach is expanded to describe how signaling networks might regulate cellular machines and evoke phenotypic behaviors.

Animals↗
PubMed2004

Computational approaches to the development of perceptual expertise.

Dog experts, ornithologists, radiologists and other specialists are noted for their remarkable abilities at categorizing, identifying and recognizing objects within their domain of expertise. A complete understanding of the development of perceptual expertise requires a combination of thorough empirical research and carefully articulated computational theories that formalize specific hypotheses about the acquisition of expertise. A comprehensive computational theory of the development of perceptual expertise remains elusive, but we can look to existing computational models from the object-recognition, perceptual-categorization, automaticity and related literatures for possible starting points. Arguably, hypotheses about the development of perceptual expertise should first be explored within the context of existing computational models of visual object understanding before considering the creation of highly modularized adaptations for particular domains of perceptual expertise.

Attention↗
PubMedDate not supplied

Transmission of the subthalamic nucleus oscillatory activity to the cortex: a computational approach.

Parkinsonian tremor is most likely due to oscillatory neuronal activities of central oscillators such as the subthalamic nucleus (STN)-external segment of the globus pallidus (GPe) pacemaker within the basal ganglia (BG). Activity from the central oscillator is proposed to be transmitted via transcortical pathways to the periphery. A computational model of the BG is proposed for simulating the transmission of the STN oscillatory activity to the cortex, based closely on known anatomy and physiology of the BG. According to the results of the simulation, for transmission of the STN oscillatory activity to the cortex, the STN oscillatory activity has to be transmitted simultaneously to the thalamus via STN-internal segment of the globus pallidus (GPi)-thalamus and STN-GPe-GPi-thalamus pathways. This transmission is controlled by the various factors such as the phase between the STN and GPe oscillatory activities, the STN oscillatory activity frequency, the low-threshold calcium spike bursts of the thalamus and the GPi spontaneous activity.

Basal Ganglia↗
PubMed1993

Computational approaches to cognition: the bottom-up view.

How can higher level aspects of cognition, such as figure-ground segregation, object recognition, selective focal attention and ultimately even awareness, be implemented at the level of synapses and neurons? A number of theoretical studies emerging out of the connectionist and the computational neuroscience communities are starting to address these issues using neural plausible models.

Animals↗
PubMed2004

A model of antipsychotic action in conditioned avoidance: a computational approach.

The selective ability of antipsychotic drugs (APDs) to attenuate conditioned avoidance responding (CAR) has been recognized for over 50 years. However, most efforts to account for this finding have been either neurochemically oriented (focusing on the neuromodulator dopamine) or behavioral, with little effort invested in uniting the two within a computational model. In this paper we propose a computational model, based on concepts from formal reinforcement learning theory, which accounts for the basic finding that noncataleptic doses of APDs disrupt avoidance without disrupting escape. The model formally separates out sensory, motor, and reward processes, and makes novel predictions pertaining to the dose- and time-dependent effects of APDs on response latencies--predictions which we verified in experimental studies using four different APDs (haloperidol, chlorpromazine, risperidone, and clozapine). The APD action in this model is most consistent with an effect on 'expected future reward'--an idea closely linked to motivational drives and consistent with several leading theories of dopamine action.

Animals↗
PubMed1993

A simple computational approach to model parameter estimation.

The desire to describe biological data using mathematical models has led to the rapid development of various analytical techniques for model identification and parameter estimation. The procedures used may be non-linear and complex, and require long calculation periods. Thus, the aid of a personal computer renders efficient the application of these rather complicated procedures. In this study we developed a simple identification programme for heparan sulfate pharmacodynamics which can be easily and rapidly implemented on a personal computer. The programme is based on an iterative algorithm performing a non-linear regression analysis by the least-square method. This programme was applied to a clinical measured variables with which it was possible to quantify the pharmacodynamic effect of heparan sulfate.

Aged↗