Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROMOLECULAR SYSTEMS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 163 records · Page 9Linked to original sources
PubMed1977

Molecular conformation of ammonium 8-anilino-1-naphthalenesulfonate hemihydrate. A fluorescent probe for thyroxine binding to thyroxine binding globulin.

The crystal and molecular structure of the ammonium hemihydrate salt of the fluorescent dye, 8-anilino-1-naphthalenesulfonic acid (ANS), has been determined. There are two conformationally distinct molecules in the triclinic P1 lattice. The anilino nitrogen of one molecule has slightly distorted planar geometry, and the overall conformation of the molecule is similar to that observed for the potassium salt of the fluorescent dye 2-p-toluidinyl-6-naphthalenesulfonic acid (TNS). The anilino nitrogen of the other molecule has slightly distorted tetrahedral geometry and the overall conformation of the molecule is similar to that observed for the thyroid hormones T3 and T4. The observation of two distinct conformational modifications of ANS in this crystal structure determination has shed light on the conformational flexibility of the ANS molecule itself and on the mode by which its acts as a competitive inhibitor in thyroid hormone transport proteins and as a signal for hydrophobic areas in macromolecular systems.

Anilino Naphthalenesulfonates↗
PubMed2005

Spatial bistability in a pH autocatalytic system: from long to short range activation.

The acid-auto-activated chlorite-tetrathionate reaction is studied in a one-side-fed spatial reactor. It was previously shown that in these conditions the unstirred reaction-diffusion system can generate oscillatory and excitable states even though under well-stirred nonequilibrium conditions only steady-state bistability is observed. Numerical simulations suggest that these temporal reaction-diffusion instabilities result from long-range activation by rapidly diffusing protons. We study here experimentally and numerically the effect of introducing into this reaction-diffusion system macromolecular carboxylate species that reduce the effective diffusivity of protons. Consistent with the original assumption, the introduction of such slow mobility proton-binding species quenches both oscillatory and excitability dynamics. Within the bistability domain the direction of the propagation of an interface between the two steady states depends on control parameter value. We elaborate on the fact that beyond a low critical concentration of macromolecular carboxylate species, the stability limit of the "thermodynamic" branch of spatial steady state does not depend on this concentration. Despite the relative simplicity of the kinetic model used in the numerical simulations, the results are in quasi-quantitative agreement with the experimental observations.

Journal Article↗
PubMed2006

Electrostatics of ligand binding: parametrization of the generalized Born model and comparison with the Poisson-Boltzmann approach.

An accurate and fast evaluation of the electrostatics in ligand-protein interactions is crucial for computer-aided drug design. The pairwise generalized Born (GB) model, a fast analytical method originally developed for studying the solvation of organic molecules, has been widely applied to macromolecular systems, including ligand-protein complexes. However, this model involves several empirical scaling parameters, which have been optimized for the solvation of organic molecules, peptides, and nucleic acids but not for energetics of ligand binding. Studies have shown that a good solvation energy does not guarantee a correct model of solvent-mediated interactions. Thus, in this study, we have used the Poisson-Boltzmann (PB) approach as a reference to optimize the GB model for studies of ligand-protein interactions. Specifically, we have employed the pairwise descreening approximation proposed by Hawkins et al.(1) for GB calculations and DelPhi for PB calculations. The AMBER all-atom force field parameters have been used in this work. Seventeen protein-ligand complexes have been used as a training database, and a set of atomic descreening parameters has been selected with which the pairwise GB model and the PB model yield comparable results on atomic Born radii, the electrostatic component of free energies of ligand binding, and desolvation energies of the ligands and proteins. The energetics of the 15 test complexes calculated with the GB model using this set of parameters also agrees well with the energetics calculated with the PB method. This is the first time that the GB model has been parametrized and thoroughly compared with the PB model for the electrostatics of ligand binding.

Ligands↗
PubMed2006

Accurate sizing of nanoparticles using confocal correlation spectroscopy.

The ability to accurately size low concentrations of nanoscale particles in small volumes is useful for a broad range of disciplines. Here, we characterize confocal correlation spectroscopy (CCS), which is capable of measuring the sizes of both fluorescent and nonfluorescent particles, such as quantum dots, gold colloids, latex spheres, and fluorescent beads. We accurately measured particles ranging in diameter from 11 to 300 nm, a size range that had been difficult to probe, owing to a phenomenon coined biased diffusion that causes diffusion times, or particle size, to deviate as a function of laser power. At low powers, artifacts mimicking biased diffusion are caused by saturation of the detector, which is especially problematic when probing highly fluorescent or highly scattering nanoparticles. However, at higher powers (>1 mW), autocorrelation curves in both resonant and nonresonant conditions show a structure indicative of an increased contribution from longer correlation times coupled with a decrease in shorter correlation times. We propose that this change in the autocorrelation curve is due to the partial trapping of the particles as they transit the probe volume. Furthermore, we found only a slight difference in the effect of biased diffusion when comparing resonant and nonresonant conditions. Simulations suggest the depth of trapping potential necessary for biased diffusion is > 1 k(B)T. Overcoming artifacts from detector saturation and biased diffusion, CCS is particularly advantageous due to its ability to size particles in the small volumes characteristic of microfluidic channels and aqueous microdroplets. We believe the method will find increasing use in a wide range of applications in measuring nanoparticles and macromolecular systems.

Computer Simulation↗
PubMed2000

Accuracy of bound peptide structures determined by exchange transferred nuclear Overhauser data: a simulation study.

The exchange-transferred NOE method to determine the three-dimensional structure of peptides bound to proteins, or other macromolecular systems, is becoming increasingly important in drug design efforts and for large or multicomponent assemblies, such as membrane receptors, where structural analysis of the full system is intractable. The exchange-transferred nuclear Overhauser effect spectroscopy (etNOESY) method allows the determination of the bound-state conformation of the peptide from the intra-molecular NOE interactions between ligand protons. Because only ligand-ligand NOEs are generally observable, the etNOESY method is restricted to fewer NOEs per residue than direct protein structure determination. In addition, the averaging of relaxation rates between free and bound states affects the measured cross-peak intensities, and possibly the accuracy of distance estimates. Accordingly, the study reported here was conducted to examine the conditions required to define a reliable structure. The program CORONA was used to simulate etNOE data using a rate-matrix including magnetic relaxation and exchange rates for two peptide-protein complexes derived from the reference complex of cAMP-dependent protein kinase ligated with a 24-residue inhibitor peptide. The results indicate that reasonably accurate peptide structures can be determined with relatively few NOE interactions when the interactions occur between non-neighboring residues. The reliability of the structural result is suggested from the pattern of NOE interactions. A structure with an accuracy of approximately 1.3 A rms difference for the main-chain atoms can be obtained when etNOE interactions between non-neighboring residues occur over the length of the peptide. The global precision is higher (approximately 0.9 A rms difference) but is not correlated to global accuracy. A local definition of precision along the backbone appears to be a good indicator of the local accuracy.

Crystallography, X-Ray↗
PubMed2001

Geometry dependent two-dimensional heteronuclear multiplet effects in paramagnetic proteins.

We report experimental observation and numerical simulation of a two-dimensional multiplet effect in the heteronuclear correlation spectrum of a paramagnetic protein that depends on molecular geometry. This effect arises as a consequence of cross-correlated relaxation involving the Curie spin relaxation and internuclear dipolar relaxation mechanisms. It also manifests itself in resolution and sensitivity improvement in transverse relaxation optimised spectroscopy (TROSY) kind of experiments. Characteristic multiplet patterns in heteronuclear coupled two-dimensional NMR spectra encode directional information for the heteronuclear bond with respect to the paramagnetic center. These patterns, which are simulated here using Redfield's relaxation theory, can be used to obtain a new type of geometry restriction for structure determination and refinement of paramagnetic macromolecular systems.

Animals↗
PubMed2004

Optimization of 13C direct detection NMR methods.

(13)C-detected experiments are still limited by their inherently lower sensitivity, as compared to the equivalent (1)H-detected experiments. Improving the sensitivity of (13)C detection methods remains a significant area of NMR research that may provide better means for studying large macromolecular systems by NMR. In this communication, we show that (13)C-detected experiments are less sensitive to the salt concentration of the sample solution than (1)H-detected experiments. In addition, acquisition can be started with anti-phase coherence, resulting in higher sensitivity due to the elimination of the final INEPT transfer step.

Carbon Isotopes↗
PubMed2000

Pathogenic strategies of enteric bacteria.

Enteric bacteria use a limited array of macromolecular systems to implement diverse pathogenic strategies. The cellular targets of several enteric virulence factors have recently been identified. The themes that have emerged from these studies include the exploitation of molecules that regulate the actin cytoskeleton and the activation of apoptotic pathways to serve the pathogen.

Bacterial Infections↗
PubMed2004

Thermodiffusion of interacting colloids. I. A statistical thermodynamics approach.

The thermal diffusion coefficient of colloids consists of two additive contributions, one related to specific interactions between the surfaces of colloidal particles with solvent molecules, and a contribution due to interactions between the colloidal particles. In the present paper, the effect of intercolloidal particle interactions on their thermodiffusive behavior is discussed within a statistical thermodynamics framework. Transport coefficients are expressed in terms of the interaction potential between the colloidal spheres. A special feature of macromolecular systems is that this interaction potential is a potential of mean force, which is temperature dependent. It is shown that under certain conditions this implicit temperature dependence gives rise to negative Soret coefficients, that is, to diffusion of macromolecules to hot regions.

Journal Article↗
PubMed2005

Calculation of the Maxwell stress tensor and the Poisson-Boltzmann force on a solvated molecular surface using hypersingular boundary integrals.

The electrostatic interaction among molecules solvated in ionic solution is governed by the Poisson-Boltzmann equation (PBE). Here the hypersingular integral technique is used in a boundary element method (BEM) for the three-dimensional (3D) linear PBE to calculate the Maxwell stress tensor on the solvated molecular surface, and then the PB forces and torques can be obtained from the stress tensor. Compared with the variational method (also in a BEM frame) that we proposed recently, this method provides an even more efficient way to calculate the full intermolecular electrostatic interaction force, especially for macromolecular systems. Thus, it may be more suitable for the application of Brownian dynamics methods to study the dynamics of protein/protein docking as well as the assembly of large 3D architectures involving many diffusing subunits. The method has been tested on two simple cases to demonstrate its reliability and efficiency, and also compared with our previous variational method used in BEM.

Algorithms↗
PubMed1972

A molecular theory of ion-conductng channels: a field-dependent transition between conducting and nonconducting conformations.

Structural and conformational requirements for an electric field-dependent transition between conducting and nonconducting macromolecular systems are: two kinetically interconvertible and energetically similar conformations, one conducting and the other nonconducting, which have axes spanning the lipid layer of biological membranes, but which have different net dipole moments along those axes. Two examples are described. A previously defined helix, the pi(6)LD-helix now termed the beta(6) (3,3)-helix, is proposed as the conducting species, and the linear peptide correlate of the cyclic hexapeptide conformation containing two beta-turns and an inversion element of symmetry is proposed as a nonconducting species. The latter is termed an anti-beta(6) (2)-spiral and contains little or no net dipole moment per turn, whereas the beta(6) (3,3)-helix contains a net dipole moment along the helix axis of about 0.5 Debye per dipeptide unit. A related conducting and nonconducting pair with large net dipole moments of opposite sign, termed syn-beta(6) (2)-spiral and beta(6) (2,4)-helix, are also described. The spiral conformations are stabilized in a lipid layer by intermolecular hydrogen bonds, leading to a linear association of transmembrane structures. A conformational transition in one member of the array could lead to destabilization of an adjacent member of the array. The conformational analysis uses a concept of cyclic conformations with linear conformational correlates. The anti-beta(6) (2)-spiral and beta(6) (3,3)-helix are derivable from the conformations of the cyclic structure [unk], whereas the syn-beta(2)-spiral and beta(6) (2,4)-helix may be derived from the cyclic structure [unk].The conformational analysis leads to the expectation that N-formyl-(L-Ala-L-Ala-Gly)(n) would form conducting channels.

Amino Acid Sequence↗
PubMed1976

Steady-state kinetic formalism applied to multienzyme complexes, oxidative phosphorylation, and interacting enzymes.

A kinetic formalism, quite generally valid for free energy transducing, steady-state, macromolecular systems in biology, is applied here to multienzyme complexes, oxidative phosphorylation, and interacting enzymes. Systems of this type, comprising several interacting subunits, each with its own discrete set of states, present no new features in principle. Hence, they may be handled by the earlier kinetic formalism without modification. However, the kinetic diagram can become quite complicated because the state of each subunit (enzyme) must be specified in order to specify any one state of the system (complex) as a whole. Cycles, forces, fluxes, free energy levels, and state probabilities are considered.

Diffusion↗
PubMed1990

Free energy changes associated with amino acid substitution in proteins.

The estimation of free energy differences from computer simulation of macromolecular systems is important for rational strategies for drug design and for protein engineering. As an example of one mutation, we have studied the free energy change resulting from the conversion of a polar group (OH) to an apolar group (CH3) in aqueous solution. We have estimated the effect of various local environments on the magnitude of the free energy difference and find that significant environmental effects are found. We have also studied the reliability of the results in detail.

Amino Acid Sequence↗
PubMed2000

Capacitive scanning dilatometry and frequency-dependent thermal expansion of polymer films

The dilatometric properties of polymer films near and above their glass-transition temperatures were explored using capacitive high-frequency detection in temperature ramping as well as in harmonic temperature cycling experiments. The broad applicability of capacitive scanning dilatometry is demonstrated by the investigation of macromolecular systems of vastly different polarity such as polystyrene, polybutadiene, and polyvinylacetate. From temperature cycling experiments the real and imaginary parts of the frequency-dependent thermal-expansion coefficient are determined in the sub-Hz regime.

Journal Article↗
PubMed2001

Relative entropy: free energy associated with equilibrium fluctuations and nonequilibrium deviations.

Using a one-dimensional macromolecule in aqueous solution as an illustration, we demonstrate that the relative entropy from information theory, Sigma(k)p(k) ln(p(k)/p(*)(k)), has a natural role in the energetics of equilibrium and nonequilibrium conformational fluctuations of the single molecule. It is identified as the free energy difference associated with a fluctuating density in equilibrium, and is associated with the distribution deviate from the equilibrium in nonequilibrium relaxation. This result can be generalized to any other isothermal macromolecular system using the mathematical theories of large deviations and Markov processes, and at the same time provides the well-known mathematical results with interesting physical interpretations.

Journal Article↗
PubMed1994

Analysis of diffuse scattering from yeast initiator tRNA crystals.

Yeast initiator tRNA crystals exhibit strong X-ray diffuse scattering. This scattering can be used to extract information about lattice-coupled and intramolecular motions in the crystals. The amplitudes and correlation distances of these motions can be estimated by calculating the diffuse scattering and comparing the results with the observed scattering. Results indicate that both anisotropic, lattice-coupled motions as well as short-range correlated local disorder in the anticodon arm contribute to the overall disorder in the crystals. These types of motions can be correlated with aspects of tRNA function. This additional information complements the results from analysis of crystallographic data and provides a more detailed picture of the structure and dynamics of the molecule. The degree to which the methodology presented here can account for the observed diffuse scattering from tRNA represents a significant step forward in the ability to use this conventionally discarded information, and encourages the ultimate extension of these ideas to a wide variety of macromolecular systems.

Journal Article↗
PubMed2000

Deconvoluting ultrafast structural dynamics: temporal resolution beyond the pulse length of synchrotron radiation.

100 picosecond X-ray snapshots visualizing the structural dynamics of macromolecular systems are now routinely available at synchrotron sources. A wealth of fundamental processes in photochemistry, condensed matter physics and biology, however, occur on considerably faster time scales. Standard experimental protocols at synchrotron sources cannot provide structural information with faster temporal resolution as these are limited by the duration of the electron bunch within the synchrotron ring. By walking the timing of femtosecond laser photolysis through a (much longer) X-ray pulse in steps of a few picoseconds, structural information on ultrafast dynamics may be retrieved from a set of X-ray scattering images, initially through deconvolution and subsequently through refinement. This experimental protocol promises immediate improvements in the temporal resolution available at synchrotron sources, facilitating the study of a number of rapid complex photochemical processes. Combined with techniques which reshape the X-ray probe pulse, the accessible temporal domain could further be extended to near-picosecond resolution.

Journal Article↗