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Results for “Models, Theoretical”

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PubMed1984

pH modulation of transient state kinetics of enzymes. I. Simple theoretical models.

The effect of proton concentration on pre-steady-state kinetics has been investigated theoretically for enzyme reactions involving the breaking of one substrate into two products. Even for the simple double-intermediate mechanism the approach to the steady state may exhibit a rather complex kinetics, which is pH-dependent. This process may even exhibit damped oscillations. A change of pH may completely change this transient kinetics and even suppresses the oscillatory regime. A simple method is presented which allows estimation of the values of the rate and ionization constants. This procedure allows one to distinguish the simple double-intermediate mechanism from a more complex process where the 'fast' binding of the substrate induces a 'slow' conformation change of the enzyme.

Enzymes↗

PubMed1990

A quantum chemical study of the enzymatic deamination of benzoadenine derivatives. A theoretical model of the interactions occurring between nucleosides and the active site of adenosine deaminase.

A theoretical study is presented, where, by using both ab initio and semi-empirical methodologies, the properties of benzoadenine derivatives as substrates of adenosine deaminase are discussed. The results suggest that lin-benzoadenine and lin-benzoadenosine can be recognized with an affinity similar to that of adenosine, but only if they are introduced about 0.12 nm deeper inside the active site of the enzyme than the natural substrate adenosine. This fact implies the existence of non-linear hydrogen bonds inside the active site of adenosine deaminase. Ab initio molecular electrostatic potential values suggest that these hydrogen bonds can exist, and have stability similar to that of linear hydrogen bonds. Finally, the great rate of deamination of lin-benzoadenine, comparable with that of adenosine despite the absence of the ribose, is explained in the context of the hypothesis that the protonation at the N1 atom is the rate-determining step of the whole deamination reaction.

Adenosine↗

PubMed1976

Influence of molecular variations of ionophore and lipid on the selective ion permeability of membranes: II. A theoretical model.

The steady-state electrical properties induced by neutral carriers of ions in lipid bilayer membranes and the time dependence of the membrane current for low applied voltages are described theoretically in terms of a model which allows for a voltage dependence of the interfacial reactions, as well as for a trapezoid shape of the internal free energy barrier for translocation of the complex. The basic features of the model are closely related to those of others presented previously (J.E. Hall, C.A. Mead & G. Szabo, 1973, J Membrane Biol. 11:75; S.B. Hladky, 1974, Biochim, Biophys. Acta 352:71, S.B. Hladky, 1975, Biochim, Biophys. Acta 375: 327; Eisenman, Krasne & Ciani, 1975, Ann. N.Y. Acad, Sci. 264:34), but the analysis of its consequences on the steady-state and nonsteady-state electrical characteristics is given here in greater detail and is extended to provide the expression for the zero-current potential in ionic gradients. It is shown that parameters, such as the width of the trapezoidal barrier, the plane of the reaction and the ratio constant of translocation across the membrane interior to the rate of constant of dissociation of the complex, can be deduced from steady-state analysis, whereas the individual values of these constants and the distance between the equilibrium positions of the complexes are deducible from relaxation measurements.

Biological Transport, Active↗

PubMed2006

Direct MRI detection of neuronal magnetic fields in the brain: theoretical modeling.

Whether MRI can be used for direct detection of neuronal activity is a matter of debate. Controversial theoretical and experimental results have been reported. Here, we present an improved current-dipole model to compute magnetic field generated by neural firing and to calculate MRI signal changes resulting from the neuronal magnetic field (NMF). Each dendrite or each unmyelinated axon was modeled as a modified current-dipole. NMF were estimated based on a synchronized activity of multiple neurons. Sensitivity of using phase and magnitude MRI to measure effects of NMF was evaluated. Our results show that NMF can potentially generate up to a few percent changes in MRI magnitude signals. Phases of MRI signal tend to be destructively added and are insensitive to NMF in the activated region when the distribution of the activated dendrites is symmetrical. Phases could be detected when the distribution of the activated dendrites is asymmetrical and on some neighboring voxels. Our modeling implies that direct MRI detection of neuronal activity is possible.

Brain↗

PubMed2006

A theoretical model to predict the low-frequency sound absorption of a helmholtz resonator array.

A theoretical method based on mutual radiation impedance is proposed to compute the sound absorption performance of a Helmholtz resonator array in the low-frequency range. Any configuration of resonator arrangement can be allowed in the method, while all the resonators may or may not be identical. Comparisons of the theoretical predictions with those done by the past studies or experiments show that the present method can accurately predict the absorption performance in more general cases.

Journal Article↗

PubMed2006

A theoretical model of the catalytic mechanism of the Delta5-3-ketosteroid isomerase reaction.

The present paper describes a theoretical approach to the catalytic reaction mechanism involved in the conversion of 5-androstene-3,17-dione to 4-androstene-3,17-dione. The model incorporates the side chains of the residues tyrosine (Tyr(14)), aspartate (Asp(38)) and aspartic acid (Asp(99)) of the enzyme Delta(5)-3-ketosteroid isomerase (KSI; EC 5.3.3.1). The reaction involves two steps: first, Asp(38) acts as a base, abstracting the 4beta-H atom (proton) from C-4 of the steroid to form a dienolate as the intermediate; next, the intermediate is reketonized by proton transfer to the 6beta-position. Each step goes through its own transition state. Functional groups of the Tyr(14) and Asp(99) side chains act as hydrogen bond donors to the O1 atom of the steroid, providing stability along the reaction coordinate. Calculations were assessed at high level Hartree-Fock theory, using the 6-31G(*) basis set and the most important physicochemical properties involved in each step of the reaction, such as total energy, hardness, and dipole moment. Likewise, to explain the mechanism of reaction, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), atomic orbital contributions to frontier orbitals formation, encoded electrostatic potentials, and atomic charges were used. Energy minima and transition state geometries were confirmed by vibrational frequency analysis. The mechanism described herein accounts for all of the properties, as well as the flow of atomic charges, explaining both catalytic mechanism and proficiency of KSI.

Androstenedione↗

PubMed2003

Complex distributions of residual stress and strain in the mouse left ventricle: experimental and theoretical models.

Most soft biological tissues, including ventricular myocardium, are not stress free when all external loads are removed. Residual stress has implications for mechanical performance of the heart, and may be an indicator of patterns of regional growth and remodeling. Cross-sectional rings of arrested ventricles opened up when a radial cut was made (initial mean opening angles were 64 +/- 17 degrees), but further circumferential cuts revealed the presence of additional residual stresses in the tissue with further opening of the rings. In normal mouse hearts, the inner half of a short-axis ring opened more than the outer half, and this change was dependent on apex-base location. At the apex the inner section vs. outer section opening angles were 226 +/- 47 degrees vs. 89 +/- 28 degrees, while at the base the same two angles were 160 +/- 30 degrees vs. 123 +/- 35 degrees. A simple theoretical cylindrical shell model with incompressible hyperelastic material properties was used to model the experimental deformations based on the cutting experiments. The model predicts different residual stress fields depending on the nature of the opening after the circumferential cut (which is done after the conventional radial cut). The observed opening angles were consistent with steep stress gradients near the endocardium compared with those predicted if the first cut was assumed to relieve all residual stresses. These results imply a more complex distribution of residual stress and strain in ventricular myocardium than previously thought.

Anatomy, Cross-Sectional↗

PubMed1981

Theoretical models for cooperative steady-state ATPase activity of myosin subfragment-1 on regulated actin.

Recent theoretical work on the cooperative equilibrium binding of myosin subfragment-1-ADP to regulated actin, as influenced by Ca2+, is extended here to the cooperative steady-state ATPase activity of myosin subfragment-1 on regulated actin. Exact solution of the general steady-state problem will require Monte Carlo calculations. Three interrelated special cases are discussed in some detail and sample computer (not Monte Carlo) solutions are given. The eventual objective is to apply these considerations to in vitro experimental data and to in vivo muscle models.

Actins↗

PubMed2000

Experimental observation, theoretical models, and biomechanical inference in the study of mandibular form.

Experimental studies and mathematical models are disparate approaches for inferring the stress and strain environment in mammalian jaws. Experimental designs offer accurate, although limited, characterization of biomechanical behavior, while mathematical approaches (finite element modeling in particular) offer unparalleled precision in depiction of strain magnitudes, directions, and gradients throughout the mandible. Because the empirical (experimental) and theoretical (mathematical) perspectives differ in their initial assumptions and their proximate goals, the two methods can yield divergent conclusions about how masticatory stresses are distributed in the dentary. These different sources of inference may, therefore, tangibly influence subsequent biological interpretation. In vitro observation of bone strain in primate mandibles under controlled loading conditions offers a test of finite element model predictions. Two issues which have been addressed by both finite element models and experimental approaches are: (1) the distribution of torsional shear strains in anthropoid jaws and (2) the dissipation of bite forces in the human alveolar process. Not surprisingly, the experimental data and mathematical models agree on some issues, but on others exhibit discordance. Achieving congruence between these methods is critical if the nature of the relationship of masticatory stress to mandibular form is to be intelligently assessed. A case study of functional/mechanical significance of gnathic morphology in the hominid genus Paranthropus offers insight into the potential benefit of combining theoretical and experimental approaches. Certain finite element analyses claim to have identified a biomechanical problem unrecognized in previous comparative work, which, in essence, is that the enlarged transverse dimensions of the postcanine corpus may have a less important role in resisting torsional stresses than previously thought. Experimental data have identified subperiosteal cortical thinning as a culprit in diminishing the role of cross-sectional geometry in conditioning the strain environment. These observations raise questions concerning the biomechanical significance of mandibular form in early hominids, fueling persistent arguments over whether gnathic morphology can be related to dietary specialization in the "robust" australopithecines. Nonmechanical explanations (e.g., tooth size or body size) for Paranthropus mandibular dimensions, however, are not compelling as competing hypotheses. Both theoretical and experimental models are in need of refinement before it is possible to conclude that the jaws of the "robust" australopithecines are not functionally linked to elevated masticatory loads.

Animals↗

PubMed2003

Artificial a theoretical model of triggered displaced aggression.

A tit-for-tat matching rule (Axelrod, 1984) describes much interpersonal behavior. Yet, in daily life a retaliatory aggressive response to a trivially mild provocation often inappropriately exceeds that expected from the matching rule. The concept of triggered displaced aggression can explain these exceptions to the matching principle. Building from the Cognitive Neoassociationistic model of aggressive behavior (Berkowitz, 1989, 1990, 1993), we developed a theoretical framework of social and personality factors that moderate and mediate the disjunctively escalated retaliation that can result from triggered displaced aggression. Major explanatory factors in our analysis of such effects are as follows: (a) aspects of the Time 1 provocation and the immediate situation in which it occurred; (b) characteristics of initial provocations and personality factors of the actor that produce the ruminative thought that will temporally extend the effects of a Time 1 provocation, allowing them to interact with a delayed Time 2 minor triggering event; and (c) actions and attributes of the target of displaced aggression that augment these effects.

Aggression↗

PubMedDate not supplied

Diffusion-weighted imaging in tissues: theoretical models.

Typical diffusion measurements use Stejskal-Tanner pulsed gradient spin echo sequences to provide information about the average diffusion and displacement profiles of particles in a sample. To derive structural information, a measured displacement profile has to be related by means of a model to the physical and geometrical properties of the tissue, such as diffusion coefficients and shapes of semi-permeable membranes of compartments in the system. The behavior of the NMR signal and the measured ADC are greatly affected by the cellular architecture of a tissue, mainly because cellular membranes are relatively impermeable to water. For long diffusion times, and small signal attenuations, ADC is relatively insensitive to how it is measured. In general, however, ADC values are not readily interpreted unless the measuring conditions are specified in detail. For given measuring conditions, ADC depends on intra- and extracellular diffusion coefficients, membrane permeabilities, cell sizes and the cellular volume fraction. If intra- and extracellular T2 relaxation rates are different enough, ADC may also depend on the relaxation properties of the system and the echo time. An improved understanding of the precise influence of these factors has been obtained by detailed consideration of theoretical and computer models that can be related to experimental data in simple systems. Further refinements of such models should advance our understanding of water diffusion in tissues.

Body Water↗

PubMed2000

Phylogenetic relationships and theoretical model of human cathepsin W (lymphopain), a cysteine proteinase from cytotoxic T lymphocytes.

The recently described cysteine proteinase cathepsin W, also known as lymphopain, which is expressed specifically by CD8+ T lymphocytes, is phylogenetically related to the cruzipain-like group of the C1 family of peptidases. We have constructed sequence alignments and a theoretical three dimensional homology model of cathepsin W. These have allowed the characterization of signature features of cathepsin W in particular and the cruzipain lineage in general. The signature features are (1) an extended loop structure, Gly 170-Trp 200, in the second or beta-sheet domain; (2) an additional disulfide bond, Cys 25/Cys 60; (3) an additional "orphan" cysteine, Cys 5; (4) an additional residue. Ala 11, inserted after the first beta-sheet sheet; and (5) an S2 pocket lined with Phe 68 and Phe 230 which explains the preference for substrates containing Leu at P2. Further, the model suggested that cathepsin W could exist as a dimer with the Cys 5 of each monomer forming a disulfide bond and the Arg 40 Phe 46 loop (RISFWDF) forming part of the dimeric interface. By comparing cathepsin W with other members of the cruzipain group and with other C1 peptidases, six conserved residues were identified which appear in general to be characteristic of the cruzipain group, and which differentiate cruzipain group members from other C1 peptidases including those of the related cathepsin L lineage. The signature residues of the cruzipain lineage are (cruzipain numbering) Asn 33, Trp 38, Ala 124, Leu 127, Leu 164, and Pro 174.

Amino Acid Sequence↗

PubMed2000

[Experimental hepatocarcinogenesis--evaluation of the significance of theoretical models. Contemporary models].

There are an increasing number of models for the study of liver cancer development with such agents as chemicals, hormones, and viruses. This process is almost always a multistep and during the long period of cancer development, discrete cells or cell populations acquire step-by step the various properties that go to make up a cancer. The hepatocarcinogenesis models are useful in identification and analysis of the preneoplastic and neoplastic alterations, as well HCC. This article presents a review of theoretical foundation and mechanisms of various models of experimental hepatocarcinogenesis as well contain a short presentation of animals practical in those experiments, principally rats. The remarkable similarities between many models with different carcinogens in animals and humans suggest the importance of such studies in understanding of molecular basis of liver cancer development.

Animals↗

PubMed1989

Theoretical modeling to predict violence in hospitalized psychiatric patients.

Research from a nursing perspective on factors related to psychiatric inpatient violence is lacking. The purpose of the study was to test a nursing theoretical framework of violence using predictive model testing. Data were collected by 57 nursing staff on 162 hospitalized patients in four hospitals. Inconsistencies in the social and therapeutic rules predicted 18% of the violent behavior. Demographic and medical variables contributing to violence were: history of violence towards others, length of hospitalization, and the diagnosis of substance abuse. The findings support the need for further research to identify nursing concepts that contribute to patient violence.

Adult↗

PubMed2004

Theoretical model to determine the effects of geometrical factors on the resorption of calcium phosphate bone substitutes.

A theoretical approach was used to determine the effect of geometrical factors on the resorption rate of calcium phosphate bone substitutes that are either dense, microporous, and/or contain spherical macropores. Two cases were considered: (a) macroporous blocks that can be invaded by resorbing cells either directly because the structure is fully open-porous, or indirectly after some resorption of the macropores walls and/or interconnections. (b) Microporous or dense blocks/granules that cannot be invaded by resorbing cells, i.e. can only be resorbed from the outside to the inside, layer by layer. The theoretical approach was based on five assumptions: (i) the pores are spherical; (ii) the pores are ordered according to a face-centered cubic packing; (iii) the resorption is surface-controlled; (iv) the resorption is only possible if the surface can be accessed by blood vessels of 50 microm in diameter; and (v) the resorption time of a given amount of calcium phosphate is proportional to the net amount of material. Based on these assumptions, the calculations showed that the resorption time of a macroporous block could be minimized at a specific pore radius. This pore radius depended (i) on the size of the bone substitute and (ii) on the interpore distance. Typical radii were in the range of 100-400 microm. These values are similar to the numerous pore size optima mentioned in the scientific literature. For microporous or dense blocks/granules, the model suggested that a relatively small radius should be preferred. Such a radius leads to an optimum combination of a high surface area favorizing resorption and the presence of large intergranular gaps favorizing blood vessel ingrowth. In that case, the optimum of granule radius is around 100-200 microm. Finally, a very good agreement was found between the predictions of the model and experimental data, i.e. the model explained in all but two cases the results with an accuracy superior to 80%. In conclusion, the model appears to be a useful tool to better understand in vivo results, and possibly better define the geometry and distribution of the pores as well as the size of a bone substitute.

Absorbable Implants↗

PubMedDate not supplied

Mechano-electric interactions in heterogeneous myocardium: development of fundamental experimental and theoretical models.

The heart is structurally and functionally a highly non-homogenous organ, yet its main function as a pump can only be achieved by the co-ordinated contraction of millions of ventricular cells. This apparent contradiction gives rise to the hypothesis that 'well-organised' inhomogeneity may be a pre-requisite for normal cardiac function. Here, we present a set of novel experimental and theoretical tools for the study of this concept. Heterogeneity, in its most condensed form, can be simulated using two individually controlled, mechanically interacting elements (duplex). We have developed and characterised three different types of duplexes: (i) biological duplex, consisting of two individually perfused biological samples (like thin papillary muscles or a trabeculae), (ii) virtual duplex, made-up of two interacting mathematical models of cardiac muscle, and (iii) hybrid duplex, containing a biological sample that interacts in real-time with a virtual muscle. In all three duplex types, in-series or in-parallel mechanical interaction of elements can be studied during externally isotonic, externally isometric, and auxotonic modes of contraction and relaxation. Duplex models, therefore, mimic (patho-)physiological mechano-electric interactions in heterogeneous myocardium at the multicellular level, and in an environment that allows one to control mechanical, electrical and pharmacological parameters. Results obtained using the duplex method show that: (i) contractile elements in heterogeneous myocardium are not 'independent' generators of tension/shortening, as their ino- and lusitropic characteristics change dynamically during mechanical interaction-potentially matching microscopic contractility to macroscopic demand, (ii) mechanical heterogeneity contributes differently to action potential duration (APD) changes, depending on whether mechanical coupling of elements is in-parallel or in-series, which may play a role in mechanical tuning of distant tissue regions, (iii) electro-mechanical activity of mechanically interacting contractile elements is affected by their activation sequence, which may optimise myocardial performance by smoothing intrinsic differences in APD. In conclusion, we present a novel set of tools for the experimental and theoretical investigation of cardiac mechano-electric interactions in healthy and/or diseased heterogeneous myocardium, which allows for the testing of previously inaccessible concepts.

Animals↗

PubMed2003

Theoretical modeling of enzyme catalytic power: analysis of "cratic" and electrostatic factors in catechol O-methyltransferase.

A comparative theoretical study of a bimolecular reaction in aqueous solution and catalyzed by the enzyme catechol O-methyltransferase (COMT) has been carried out by a combination of two hybrid QM/MM techniques: statistical simulation methods and internal energy minimizations. In contrast to previous studies by other workers, we have located and characterized transition structures for the reaction in the enzyme active site, in water and in a vacuum, and our potential of mean force calculations are based upon reaction coordinates obtained from features of the potential energy surfaces in the condensed media, not from the gas phase. The AM1/CHARMM calculated free energy of activation for the reaction of S-adenosyl methionine (SAM) with catecholate catalyzed by COMT is 15 kcal mol(-1) lower the AM1/TIP3P free-energy barrier for the reaction of the trimethylsulfonium cation with the catecholate anion in water at 300 K, in agreement with previous estimates. The thermodynamically preferred form of the reactants in the uncatalyzed model reaction in water is a solvent-separated ion pair (SSIP). Conversion of the SSIP into a contact ion pair, with a structure resembling that of the Michaelis complex (MC) for the reaction in the COMT active site, is unfavorable by 7 kcal mol(-1), largely due to reorganization of the solvent. We have considered alternative ways to estimate the so-called "cratic" free energy for bringing the reactant species together in the correct orientation for reaction but conclude that direct evaluation of the free energy of association by means of molecular dynamics simulation with a simple standard-state correction is probably the best approach. The latter correction allows for the fact that the size of the unit cell employed with the periodic boundary simulations does not correspond to the standard state concentration of 1 M. Consideration of MC-like species allows a helpful decomposition of the catalytic effect into preorganization and reorganization phases. In the preorganization phase, the substrates are brought together into the MC-like species, either in water or in the enzyme active site. In the reorganization phase, the roles of the enzymic and aqueous environments may be compared directly because reorganization of the substrate is about the same in both cases. Analysis of the electric field along the reaction coordinate demonstrates that in water the TS is destabilized with respect to the MC-like species because the polarity of the solute diminishes and consequently the reaction field is also decreased. In the enzyme, the electric field is mainly a permanent field and consequently there is only a small reorganization of the environment. Therefore, destabilization of the TS is lower than in solution, and the activation barrier is smaller.

Catalysis↗

PubMed1998

A retroductive theoretical model of the pathway to chemical dependency in nurses.

Much of the research on chemical dependency in nurses over the past 25 years has been a-theoretical and has tended to focus on descriptive characteristics of nurses. This field of study lacks systematic knowledge building and a useful theoretical base. This article focuses on the development of a middle range theory that begins to explicate the transactions of the chemically dependent nurse with the environment and the process through which nurses become addicted. Steiner's theory models approach using retroductive inference was the method selected to develop the theory. Theoretical work from Bandura, Jessor, and Pender were used as source theories to develop the middle range theory presented.

Female↗