SEARCH · PubMed Health

Results for “MACROMOLECULAR SYSTEMS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2004

A mobile loop order-disorder transition modulates the speed of chaperonin cycling.

Molecular machines order and disorder polypeptides as they form and dissolve large intermolecular interfaces, but the biological significance of coupled ordering and binding has been established in few, if any, macromolecular systems. The ordering and binding of GroES co-chaperonin mobile loops accompany an ATP-dependent conformational change in the GroEL chaperonin that promotes client protein folding. Following ATP hydrolysis, disordering of the mobile loops accompanies co-chaperonin dissociation, reversal of the GroEL conformational change, and release of the client protein. "High-affinity" GroEL mutants were identified by their compatibility with "low-affinity" co-chaperonin mutants and incompatibility with high-affinity co-chaperonin mutants. Analysis of binding kinetics using the intrinsic fluorescence of tryptophan-containing co-chaperonin variants revealed that excessive affinity causes the chaperonin to stall in a conformation that forms in the presence of ATP. Destabilizing the beta-hairpins formed by the mobile loops restores the normal rate of dissociation. Thus, the free energy of mobile-loop ordering and disordering acts like the inertia of an engine's flywheel by modulating the speed of chaperonin conformational changes.

Adenosine Triphosphate↗

PubMed2006

Monitoring protein aggregation during thermal unfolding in circular dichroism experiments.

Thermal unfolding monitored by spectroscopy or calorimetry is widely used to determine protein stability. Equilibrium thermodynamic analysis of such unfolding is often hampered by its irreversibility, which usually results from aggregation of thermally denatured protein. In addition, heat-induced protein misfolding and aggregation often lead to formation of amyloid-like structures. We propose a convenient method to monitor in real time protein aggregation during thermal folding/ unfolding transition by recording turbidity or 90 degrees light scattering data in circular dichroism (CD) spectroscopic experiments. Since the measurements of turbidity and 90 degrees light scattering can be done simultaneously with far- or near-UV CD data collection, they require no additional time or sample and can be directly correlated with the protein conformational changes monitored by CD. The results can provide useful insights into the origins of irreversible conformational changes and test the linkage between protein unfolding or misfolding and aggregation in various macromolecular systems, including globular proteins and protein-lipid complexes described in this study, as well as a wide range of amyloid-forming proteins and peptides.

Asparaginase↗

PubMed2005

Time-resolved spectroscopy of organic dendrimers and branched chromophores.

Organic dendrimers have been considered for a number of optical applications and are now of great interest for the purpose of enhanced nonlinear optical effects. In order to understand the mechanism of the enhanced effects in branched structures it is important to probe the fundamental excitations and the degree of intramolecular interactions utilizing various spectroscopic techniques. In this review, the nonlinear optical and excited state dynamics of different dendritic and other branching chromophore structures are discussed. The methods of two-photon absorption, time-resolved fluorescence, transient absorption, and three-pulse photon echo peak shift are discussed in regards to the degree of intramolecular coupling in the macromolecular systems. These techniques are also used for a comparison of the dynamics in the linear molecular analog systems as well. Thus, this review focuses on the aspect of intramolecular interactions in a branched system and its importance to enhanced nonlinear optical effects useful for modern optical devices.

Absorption↗

PubMed2005

Fourier transform infrared vibrational spectroscopic imaging: integrating microscopy and molecular recognition.

The recent development of Fourier transform infrared (FTIR) spectroscopic imaging has enhanced our capability to examine, on a microscopic scale, the spatial distribution of vibrational spectroscopic signatures of materials spanning the physical and biomedical disciplines. Recent activity in this emerging area has concentrated on instrumentation development, theoretical analyses to provide guidelines for imaging practice, novel data processing algorithms, and the introduction of the technique to new fields. To illustrate the impact and promise of this spectroscopic imaging methodology, we present fundamental principles of the technique in the context of FTIR spectroscopy and review new applications in various venues ranging from the physical chemistry of macromolecular systems to the detection of human disease.

Algorithms↗

PubMed2005

WEBnm@: a web application for normal mode analyses of proteins.

BACKGROUND: Normal mode analysis (NMA) has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes) describe the largest movements in a protein and are the ones that are functionally relevant. RESULTS: We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on http://www.bioinfo.no/tools/normalmodes. We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example. CONCLUSION: We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains.

Algorithms↗

PubMed2002

Molecular dynamics simulation for ligand-receptor studies. Carbohydrates interactions in aqueous solutions.

The review deals with the problem of the study of ligand-receptor interactions and the use of Molecular Dynamics (MD) simulation to approach such a problem. After a short review of the fundamentals of MD we describe the medium in which all biology takes place, water. Emphasis is put on the water models appropriate for simulation of macromolecular systems explicitly including the water molecules. We consider the quality of the water model both in terms of simplicity and performance to describe the liquid water properties. Heavy water, although not a biologically viable medium, is considered since many experiments make use of it as a solvent. Sweetness of carbohydrates is considered as an example of the procedure suitable to characterize active sites on the ligands. Consideration is given to the computation of the binding constants through molecular dynamics. The computation of the Free Energy is described and illustrated. The potentiality of MD for studies of ligand-receptor interactions is limited by the computer resources, for even with large computing facilities the need of relatively long simulation times severely restricts the study of large systems. A method is described in which several shells are treated at different levels of approximation, form mechanical response and mean electrical field to quantum mechanics, through stochastic dynamics and atomic classical MD. The review closes with a brief account of the perspectives of the method.

Binding Sites↗

PubMedDate not supplied

[Self-diffusion of water into silk fibers from magnetic field pulse gradient data].

Self-diffusion of water was studied in fibers of natural silk (Bombyx mori) with a water content of 0.18 g H2O/g dried material. Self-diffusion measurements were conducted by pulsed gradient of magnetic field (stimulated echo) at diffusion times from 10 to 200 mc. The dependence of experimental diffusion coefficients Dexp = f(delta) (observed decrease when delta increased) was determined to be responsible for the restricted diffusion. A model of planar and regularly spaced permeable barriers to diffusion of water molecules was applied to estimate the barrier spacing a and the permeability constant p. The maximal value of Dexp (at short diffusion time) in B. mori silk fibres was about 0.06 of the value of Dexp in bulk free water. The results obtained are compared to literature data on self-diffusion of water in hydrated biopolymer fibers and are discussed in connection with molecular mobility in natural macromolecular systems with low water content.

Diffusion↗

PubMed2003

Mechanism of cross-bridge detachment in isometric force relaxation of skeletal and cardiac myofibrils.

Skeletal and cardiac muscle relaxation is governed by the interplay between two macromolecular systems: (i) membrane bound Ca2+ transport proteins and (ii) sarcomeric proteins. Photolysis experiments in skinned muscle preparations and fast solution switching studies in single myofibrils offer means for isolating sarcomeric mechanisms of relaxation from those related to myoplasmic Ca2+ removal. Single myofibril experiments have recently shown that cross-bridge mechanics and detachment kinetics are the major determinants of the time course of relaxation. Full force decay in myofibrils occurs in two phases: a slow one followed by a rapid one. The latter is initiated by sarcomere 'give' and dominated by inter-sarcomere dynamics while the former occurs under nearly isometric conditions. Strong evidence has been found that the slow rate of force decay in myofibril relaxation reflects the rate at which cross-bridges leave force-generating states under isometric conditions. Dissection of chemo-mechanical transduction process in myofibrils indicates that both forward and backward transitions of cross-bridges from force-generating to non-force-generating states contribute to muscle relaxation.

Animals↗

PubMed2005

[Quantitative analysis of complicated casein hydrolysates by high performance size exclusion chromatography].

The enzymatic hydrolysates of casein are so complicated that there has no effective method for quantitative analysis. On the basis of membrane separation and high performance size exclusion chromatography (HPSEC), standard peptides with different relative molecular mass ranges were prepared, and the linear relationships between mass concentration of the standard peptides and the corresponding peak areas were established. Consequently, mass concentration of the different hydrolysates at different reaction time can be accurately calculated. The combination of chromatography and membrane separation is of great importance to the quantitative analysis of the complicated hydrolysates, which can be also applied to the other macromolecular systems, such as carbohydrates.

Amino Acid Sequence↗

PubMed1991

Structural interpretation of fluorescence resonance-energy transfer measurements.

Fluorescence resonance-energy transfer (FRET) has been widely used to determine distance information in macromolecular systems. However, little has been written about methods for combining FRET distances into coherent structural models. I argue that the methods used so far are inappropriate. This paper describes an algorithm specifically tailored for finding structures from FRET measurements. This algorithm finds structures which fit the experimentally measured parameter, the efficiency of energy transfer, rather than derived distances. The algorithm was implemented in Mathematica and applied to FRET distances obtained for the contractile protein actin. The approach used is applicable to other experimental techniques which measure distances between a relatively small number of loci.

Energy Transfer↗

PubMedDate not supplied

Acid-base and oxidation-reduction relationships.

pH, the symbol for "hydrogen-ion concentration", is a series of dimensionless "units" that have only general significance. The author shows that, when considered on the basis of the relationship to oxidation-reduction, the relative significance of any pair of coordinates becomes more significant. However, the theoretical relationship as currently accepted by the Nernst equation, i.e. a shift of 59.1 milivolts for each shift of 1.0 pH, does not apply to macromolecular systems, such as in vivo. The author solved this difficulty by plotting the corrdinates graphically by bisecting pH relationships at 7.0 and oxidation-reduction relationships at Eh 0.0 milivolts, forming four quadrants. With this scheme the significance of any pair of coordinates can be readily recognized. The application of this method to biology and medicine is shown in the companion paper "pH and Eh relationships in the body".

Hydrogen-Ion Concentration↗

PubMedDate not supplied

pH and Eh relationships in the body.

This report concerns application of the graphical method for representing pH and Eh relationships in macromolecular systems (see previous paper) to in vivo studies. The author presents reasons for concluding that controlled measurements of urine are satisfactory indicators of changes in pH and Eh in the body whereas blood studies remain relatively constant. The original concept had to be modified because of two little known "reversing phenomena". One is well known to physicians as the "acid rebound" because of the acid reaction of urine when an excess of a base is administered. This is a paradox because it would be expected to be more alkaline. The second phenomenon occurs following hyperoxidation, such as in narcotic addiction, and results in reduction. Both hyperalkalinity and hyperoxidation result in an acid reaction. The author concludes that they are phases of a single phenomenon. It is the basis for "Chapman's law": Unfavorable effects on the body cause the urine pH and Eh to shift away from normal whereas favorable effects cause them to shift toward normal.

Acid-Base Equilibrium↗

PubMedDate not supplied

Macromolecular transport by the middle ear and its lymphatic system.

The macromolecular transport in the middle ear mucosa of the guinea pig was investigated by means of light and electron microscopy using tracer substances such as Evans blue, India ink, and horseradish peroxidase (HRP). HRP particles were readily taken up by the middle ear mucosa and Eustachian tube. They were absorbed by all cell types, including ciliated, secretory and nonsecretory cells. The particles were first taken up by the pinocytotic vesicles and then transported into the intercellular spaces by reverse pinocytosis. These particles were transported toward the connective tissue through the basilar membrane. Some of the tracer particles were engulfed by the tissue histiocytes, but most of the particles entered into lymphatic and blood capillaries. By Evans blue instillation of the bulla, the retroauricular and junctional lymph nodes were positively identified as those draining the middle ear and the Eustachian tube. When HRP was used, the tracer particles were detected in the ipsilateral retroauricular and junctional lymph nodes as early as 5 minutes following the tympanic instillation. HRP in these lymph nodes were mainly found in the specific granules of the macrophages.

Animals↗

PubMed2005

Development of a fully automated macromolecular crystallization/observation robotic system, HTS-80.

A robotic system has been developed to be used for macromolecular crystallization and observation in typical university laboratories with a research focus on protein crystallography. The system consists of three major parts: a dispenser unit, a storage unit and an observation unit. This system is designed to automatically perform all of the processes involved in crystallization and observation without requiring any manual operations. The dispenser and observation units can carry out both sitting-drop vapor-diffusion procedures and microbatch procedures. With this system, the procedures are controlled by a personal computer running GUI-based software. After the dispensing of protein solution into the crystallization plates, they are automatically transferred to the storage units, followed by automatic observation according to a required schedule with arbitrary intervals. At each stage of crystallization, droplets in the crystallization plates are examined by original image-processing software in order to evaluate the appearance of the crystals.

Crystallization↗

PubMed1967