Simulation of an inhibitory equilibrium system. Aberrant proteinic target sizes as obtained by radiation inactivation.
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ABSTRACT:
SUBMITTER: Swillens S
PROVIDER: S-EPMC1144171 | biostudies-other | 1984 Aug
REPOSITORIES: biostudies-other
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Project description:Radiation inactivation of complex enzymic systems is currently used to determine the enzyme size and the molecular organization of the components in the system. We have simulated an equilibrium model describing the regulation of enzyme activity by association of the enzyme with a regulatory unit. It is assumed that, after irradiation, the system equilibrates before the enzyme activity is assayed. Our theoretical results show that the target-size analysis of these numerical data leads to a bad estimate of the enzyme size. Moreover, some implicit assumptions such as the transfer of radiation energy between non-covalently bound molecules should be verified before interpretation of target-size analysis. It is demonstrated that the apparent target size depends on the parameters of the system, namely the size and the concentration of the components, the equilibrium constant, the relative activities of free enzyme and enzymic complex, the existence of energy transfer, and the distribution of the components between free and bound forms during the irradiation.
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Project description:The system-size dependence of computed mutual diffusion coefficients of multicomponent mixtures is investigated, and a generalized correction term is derived. The generalized finite-size correction term was validated for the ternary molecular mixture chloroform/acetone/methanol as well as 28 ternary LJ systems. It is shown that only the diagonal elements of the Fick matrix show system-size dependency. The finite-size effects of these elements can be corrected by adding the term derived by Yeh and Hummer (J. Phys. Chem. B 2004, 108, 15873-15879). By performing an eigenvalue analysis of the finite-size effects of the matrix of Fick diffusivities we show that the eigenvector matrix of Fick diffusivities does not depend on the size of the simulation box. Only eigenvalues, which describe the speed of diffusion, depend on the size of the system. An analytic relation for finite-size effects of the matrix of Maxwell-Stefan diffusivities was developed. All Maxwell-Stefan diffusivities depend on the system size, and the required correction depends on the matrix of thermodynamic factors.
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Project description:ObjectiveTo investigate the usefulness of the 3DVH software with an ArcCHECK 3D diode array detector in newly designed plans with various target sizes.MethodsThe isocenter dose was measured with an ion-chamber and was compared with the planned and 3DVH predicted doses. The 2D gamma passing rates were evaluated at the diode level by using the ArcCHECK detector. The 3D gamma passing rates for specific regions of interest (ROIs) were also evaluated by using the 3DVH software. Several dose-volume histograms (DVH)-based predicted metrics for all structures were also obtained by using the 3DVH software.ResultsThe isocenter dose deviation was <1% in all plans except in the case of a 1 cm target. Besides the gamma passing rate at the diode level, the 3D gamma passing rate for specific ROIs tended to decrease with increasing target size; this was more noticeable when a more stringent gamma criterion was applied. No correlation was found with the gamma passing rates and the DVH-based metrics especially in the ROI with high-dose gradients.ConclusionsDelivery quality assurance by using 3DVH and ArcCHECK can provide substantial information through a simple and easy approach, although the accuracy of this system should be judged cautiously.
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Project description:The target size of neurotoxic esterase (NTE), the putative target site for the initiation of organophosphorus-compound-induced delayed neurotoxicity, and acetylcholinesterase (AChE) from hen brain were examined by determining the rate at which the activities of the esterases were destroyed by ionizing irradiation. Samples of hen brain were prepared by slowly drying a microsomal preparation under vacuum. The dried samples were then irradiated with electrons from a 1 MeV Van de Graaff generator. The doses ranged from 0 to 28 Mrad. The radiation doses were calibrated by the rate of inactivation of T1-bacteriophage plaque induction. Following the irradiation procedure, the samples were resuspended in buffer and enzymic activity was measured. The target size of NTE from hen brain was determined to be about 105 kDa, whereas hen brain AChE was found to have a target size of about 53 kDa. The target size of NTE was found to be similar in experiments with rat brain and cat brain. In addition, commercial preparations of electric-eel electric-organ AChE and horse serum butyrylcholinesterase were found to have target sizes that were identical with each other, and also were very similar to that of AChE from hen brain.
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Project description:The recent COVID-19 pandemic spread across the globe has raised the concern about the possible transmission of viruses through food packaging material during domestic and international trade. Therefore, mitigation strategies are needed to address these safety issues. Preliminary in-silico study showed that interactions between food packaging material and viral surface proteins were possibly hydrophobic in nature with most favourable interaction having a binding free energy of -5.24 kcal/mol. Since these interactions can cause viruses to adsorb on the food packets and get transmitted during supply chain, it is necessary to inactivate the viruses. In this context, efficacy of gamma irradiation in inactivating the viruses on the food packaging material was assessed. For this simulation study P1 (virulent) bacteriophage of E. coli was used as a model system. Gamma irradiation of food packets at an absorbed dose >8 kGy was found to completely inactivate the infectivity of P1(virulent) bacteriophage when co-cultured with E. coli host and assayed for viral plaque formation. Reduction in infectivity of P1(vir) phage was more prominent at ambient temperature (25 ± 2 °C) as compared to cold temperature (6 ± 2 °C) when assayed after storage (one week). Gamma irradiation (2 kGy) completely inactivated the virus particles on food packets when stored for 1 week at both the above temperatures. It is thus proposed that gamma irradiation (2 kGy) can possibly be integrated as a final treatment of the packaged food products to rule out the possibility of viral transmission. However, the efficacy of radiation processing against different pathogenic viruses needs to be determined prior to actual commercial deployment.
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Project description:Renal brush-border membrane vesicles from rat kidney cortex were irradiated in frozen state with a gamma-radiation source. Initial rates of influx into these vesicles were estimated for substrates such as L-glutamic acid, L-alanine, L-proline and L-leucine to establish the molecular sizes of their carriers. Transport was measured in initial-rate conditions to avoid artifacts arising from a decrease in the driving force caused by a modification of membrane permeability. Initial rates of Na(+)-independent uptakes for those four substrates appeared unaffected in the dose range used (0-6 Mrad), indicating that the passive permeability of the membrane towards these substrates was unaffected. However, at higher doses of irradiation the Na+ influx and the intravesicular volume evaluated by the uptake of glucose at equilibrium were altered by radiation. Thus Na(+)-dependent influx values were corrected for volume changes, and the corrected values were used to compute radiation-inactivation sizes of the transport systems. Their respective values for L-glutamic acid, L-proline, L-leucine and L-alanine carriers were 250, 224, 293 and 274 kDa. The presence of the free-radicals scavenger benzoic acid in the frozen samples during irradiation did not affect the uptake of glucose, phosphate and alkaline phosphatase activity. These results indicate that freezing samples in a cryoprotective medium was enough to prevent secondary inactivation of transporters by free radicals. Uptakes of beta-alanine and L-lysine were much less affected by radiation. The radiation-inactivation size of the Na(+)-dependent beta-alanine carrier was 127 kDa and that of the L-lysine carrier was 90 kDa.
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Project description:The functional-unit molecular size of the Na+/bile acid cotransport system and the apparent target size of the bile-acid-binding proteins in brush-border membrane vesicles from rabbit ileum were determined by radiation inactivation with high-energy electrons. The size of the functional transporting unit for Na(+)-dependent taurocholate uptake was determined to 451 +/- 35 kDa, whereas an apparent molecular mass of 434 +/- 39 kDa was measured for the Na(+)-dependent D-glucose transport system. Proteins of 93 kDa and 14 kDa were identified as putative protein components of the ileal Na+/bile acid cotransporter in the rabbit ileum, whereas a protein of 87 kDa may be involved in passive intestinal bile acid uptake. Photoaffinity labelling with 3- and 7-azi-derivatives of taurocholate revealed a target size of 229 +/- 10 kDa for the 93 kDa protein, and 132 +/- 23 kDa for the 14 kDa protein. These findings indicate that the ileal Na+/bile acid co-transport system is in its functional state a protein complex composed of several subunits. The functional molecular sizes for Na(+)-dependent transport activity and the bile-acid-binding proteins suggest that the Na+/bile acid co-transporter from rabbit ileum is a homotetramer (AB)4 composed of four AB subunits, where A represents the integral 93 kDa and B the peripheral 14 kDa brush-border membrane protein.
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