Fundamental Molecular Parameters Research Articles

Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum

Antibody profiling is a fundamental component of understanding the humoral response in a wide range of disease areas. Most currently used approaches operate by capturing antibodies onto functionalised surfaces. Such measurements of surface binding are governed by an overall antibody titre, while the two fundamental molecular parameters, antibody affinity and antibody concentration, are challenging to determine individually from such approaches. Here, by applying microfluidic diffusional sizing (MDS), we show how we can overcome this challenge and demonstrate reliable quantification of alloantibody binding affinity and concentration of alloantibodies binding to Human Leukocyte Antigens (HLA), an extensively used clinical biomarker in organ transplantation, both in buffer and in crude human serum. Capitalising on the ability to vary both serum and HLA concentrations during MDS, we show that both affinity and concentration of HLA-specific antibodies can be determined directly in serum when neither of these parameters is known. Finally, we provide proof of principle in clinical transplant patient sera that our assay enables differentiation of alloantibody reactivity against HLA proteins of highly similar structure, providing information not attainable through currently available techniques. These results outline a path towards detection and in-depth profiling of humoral immunity and may enable further insights into the clinical relevance of antibody reactivity in clinical transplantation and beyond.

Energy Renormalization for Coarse‐Graining Polymers with Different Fragilities: Predictions from the Generalized Entropy Theory

AbstractBottom‐up prediction of physical performance of glass‐forming (GF) polymers via coarse‐grained (CG) modeling is challenging because these CG models normally experience significantly altered dynamics that strongly vary with temperature. Building upon the recently developed energy‐renormalization (ER) coarse‐graining method based on molecular dynamics simulations, generalized entropy theory (GET) is employed to theoretically investigate the influence of fundamental molecular parameters on CG modeling of polymers having different glass “fragilities” Taking a linear polymer melt as a model system within the GET framework, it is shown that the chain bending rigidity and cohesive interaction play critical roles in the glass formation of polymers and their CG analogs. To coarse‐grain polymers having a higher fragility index, it requires greater magnitudes of ER factor εCG to rescale the cohesive interaction strength under coarse‐graining and thus recover the atomistic relaxation dynamics over a wide temperature range. The GET further predicts that a higher degree of coarse‐graining generally requires greater magnitudes of εCG due to the influence of loss of configuration entropy sc on the dynamics. GET analyses herein theoretically demonstrate the efficacy of the ER method toward building a multiscale temperature transferable modeling framework for GF polymers, and confirm the importance of preserving sc in CG modeling of dynamics of soft materials.

Experiments and Simulations of Complex Sugar-Based Coil-Brush Block Polymer Nanoassemblies in Aqueous Solution.

In this work, we investigated the fundamental molecular parameters that guide the supramolecular assembly of glucose-based amphiphilic coil-brush block polymers in aqueous solution and elucidated architecture-morphology relationships through experimental and simulation tools. Well-defined coil-brush polymers were synthesized through ring-opening polymerizations (ROP) of glucose carbonates to afford norbornenyl-functionalized poly(glucose carbonate) (NB-PGC) macromonomers, followed by sequential ring-opening metathesis polymerizations (ROMP) of norbornene N-hydroxysuccinimidyl (NHS) esters and the NB-PGC macromonomers. Variation of the macromonomer length and grafting through ROMP conditions allowed for a series of coil-brush polymers to be synthesized with differences in the brush and coil dimensions, independently, where the side chain graft length and brush backbone were used to tune the brush, and the coil block length was used to vary the coil. Hydrolysis of the NHS moieties gave the amphiphilic coil-brush polymers, where the hydrophilic-hydrophobic ratios were dependent on the brush and coil relative dimensions. Experimental assembly in solution was studied and found to yield a variety of structurally dependent nanostructures. Simulations were conducted on the solution assembly of coil-brush polymers, where the polymers were represented by a coarse-grained model and the solvent was represented implicitly. There is qualitative agreement in the phase diagrams obtained from simulations and experiments, in terms of the morphologies of the assembled nanoscopic structures achieved as a function of coil-brush design parameters ( e.g., brush and coil lengths, composition). The simulations further showed the chain conformations adopted by the coil-brush polymers and the packing within these assembled nanoscopic structures. This work enables the predictive design of nanostructures from this glucose-based coil-brush polymer platform while providing a fundamental understanding of interactions within solution assembly of complex polymer building blocks.

Direct and Absolute Quantification of over 1800 Yeast Proteins via Selected Reaction Monitoring

Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative protein changes are available, defining robust absolute values in copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800 Saccharomyces cerevisiae proteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any previous study. This was achieved by careful design of over 100 QconCAT recombinant proteins as standards, defining 1167 proteins in terms of copies per cell and upper limits on a further 668, with robust CVs routinely less than 20%. The selected reaction monitoring-derived proteome is compared with existing quantitative data sets, highlighting the disparities between methodologies. Coupled with a quantification of the transcriptome by RNA-seq taken from the same cells, these data support revised estimates of several fundamental molecular parameters: a total protein count of ∼100 million molecules-per-cell, a median of ∼1000 proteins-per-transcript, and a linear model of protein translation explaining 70% of the variance in translation rate. This work contributes a “gold-standard” reference yeast proteome (including 532 values based on high quality, dual peptide quantification) that can be widely used in systems models and for other comparative studies.

Comparative sensitivity analysis of transport properties and reaction rate coefficients

AbstractTransport properties of chemical species are required for many combustion models. A sensitivity analysis is conducted to assess the significance of transport properties and their underlying molecular parameterizations for atmospheric pressure premixed laminar flames for three different fuels and two different approaches to transport property calculations. The analysis is performed at both the macroscopic level of Arrhenius A‐factors and transport coefficients as well as at the molecular scale. First‐ and second‐order sensitivities of reactant, intermediate, and product species concentrations, temperature, and flame velocity were calculated with respect to various parameters, all within the mixture approximation using ADIFOR 2.0, a software package that supports exact differentiation. Parameters considered were the binary diffusion coefficients, pure species thermal conductivity coefficients, and thermal diffusion ratios. The more fundamental molecular parameters: collision diameters, well depths, dipole moments, polarizabilities, and the rotational relaxation collision numbers were also considered.Influential transport properties are found to be as important in flame modeling as influential reaction rates, and both should be taken into account when building chemical mechanisms. Transport parameter importance was found to vary according to the independent variable being considered and the flame type. Magnitudes of sensitivities appear to be more influenced by the underlying molecular parameters than the approach used to compute the transport properties. The number of significant sensitivities to transport parameters increases for the progression: flame temperature, flame velocity, reactant species, product species, and intermediate radical species. Many dependent variables have significant sensitivities to the pure species thermal conductivities of N2, O2, and the fuel. At the molecular level, large sensitivities to the collision diameters of several species are also observed, but significant sensitivity to well depths, although observed is less and more rare. Large sensitivities are not observed to the rotational relaxation collision number, the dipole moment, or to the molecular polarizability. Second‐order sensitivities are significant for a number of dependent variables. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 538–553, 2005

Binding behaviour and conformational properties of globular proteins in the presence of immobilised non-polar ligands used in reversed-phase liquid chromatography

The thermodynamic and extra-thermodynamic dependencies of five types of cytochrome c in water–acetonitrile mixtures of different composition in the presence of immobilised n-octyl ligands as a function of temperature from 278 K to 338 K have been investigated. The corresponding enthalpic, entropic and heat capacity parameters, Δ H assoc ° , Δ S assoc ° and Δ C p ° , have been evaluated from the observed non-linear Van’t Hoff plots of these globular proteins in these heterogeneous systems. The relationships between the free energy dependencies, various molecular parameters and extra-thermodynamic dependencies (empirical correlations) of these protein–non-polar ligand interactions have also been examined. Thus, the involvement of enthalpy-entropy compensation effects has been documented for the binding of these cytochrome cs to solvated n-octyl ligands. Moreover, the results confirm that this experimental approach permits changes in molecular surface area due to the unfolding of these proteins on association with non-polar ligands as a function of temperature to be correlated with other biophysical properties. This study thus provides a general procedure whereby the corresponding free energy dependencies of globular proteins on association with solvated non-polar ligands in heterogeneous two-phase systems can be quantitatively evaluated in terms of fundamental molecular parameters.

Spectroscopic determination of fundamental molecular parameters for methanol and its isotopomers

An approach is presented, in which such fundamental molecular parameters as geometric structural parameters and potential ones are used to analyze observed spectra of a molecule with an internal rotor. As an example, geometric structural parameters, harmonic vibrational force constants, barrier heights to the internal rotation, and barrier derivatives with respect to molecular internal coordinates are determined by fitting them to observed torsion–rotational spectra for methanol and its isotopomers. By using these determined parameters, all the unreduced torsion–rotational molecular constants up to fourth order are calculated numerically.

On the physical interpretation of torsion–rotational parameters for CH 3OD isotopomers

Using the formulation (Phys. Lett. A 207 (1995) 203) of the centrifugal distortion effects in terms of the potential parameters for a molecule that contains a threefold symmetric internal rotor, molecular parameters have been determined for the 12 C and 13 C isotopomers of CH 3OD with O-16, 17 and 18. The calculated parameters, especially the constants that represent interactions between torsion and rotation, are used to interpret the relationships among the terms in the reduced Hamiltonian and in the analysis of the observed torsion–rotational spectrum. Molecular parameters are calculated from several potential energy functions for methanol isotopomers to check the quality of these potentials. The dependence of torsion–rotational parameters on the mass of atom and the geometric parameters are addressed by comparisons of calculated values for various isotopomers of CH 3OD. The parameters are compared with the parameters that were obtained from several global fits to experimental spectrum data. The good agreement between the calculated torsion–rotational parameters and those derived from the global fits demonstrates that the derived formulae provide a useful tool for understanding the physical origins of the Hamiltonian parameters and the dependence of torsion–rotational parameters on fundamental molecular parameters.

Artificial neural networks for the prediction of liquid viscosity, density, heat of vaporization, boiling point and Pitzer's acentric factor Part I. Hydrocarbons

A predictive method, based on artificial neural networks (ANN) and equilibrium physical properties, has been developed for the viscosity, density, heat of vaporization, boiling point and Pitzer's acentric factor for pure organic liquid hydrocarbons over a wide range of temperatures (Treduced≈0.45–0.7). A committee ANN was trained, using ten physicochemical and structural properties combined with absolute temperature as its inputs, to correlate and predict viscosity. A group of 281 compounds, of diverse structure, were arbitrarily ordered into a set of 200 compounds, which were used to train the committee ANN, and a group of 81 compounds, which were used to test the predictive performance of the committee ANN. The viscosity and input data for each individual compound was compiled on average at forty different temperatures, ranging from the melting points to the boiling points for each of the chosen compounds. The mean average absolute deviation in viscosity, predicted by the committee ANN, was ±7.9% which reduces to ±6.5% when the correlated data is also considered. These values are almost a factor of 2 better than other predictive methods and are below the mean average absolute experimental deviation of approximately ±10%, quoted by the DIPPR reference database (AIChE, 1994). In a preliminary study a separate committee ANN was also used to predict the viscosity of the highly polar and hyrdogen bonding compounds, aliphatic acids, alcohols and amines. The predicted mean average absolute deviation for the amines, alcohols and aliphatic acids was ±8.9%. Although this paper deals predominantly with liquid viscosity the same methodology was applied to liquid density, heat of vaporization, boiling point and Pitzer's acentric factor. The predicted mean average absolute deviation for these equilibrium properties was ±0.71%, ±1.04%, ±0.39% and ±5.6% respectively. An attempt has also been made to use the ANN to determine the hierarchical dependencies of viscosity on fundamental molecular and structural parameters.

Modeling of unsaturated polyester prepolymer structures. I. Chain branches and overall chain end numbers

A review on the synthesis of unsaturated polyester (UP) prepolymers showed that Ordelt saturation (reaction of hydroxyl groups with double bonds) is the major effect that may cause formation of chain branches and then result in an uncertainty of chain end number or functionality. A model has been derived in this work to estimate the number of chain branches and the number of chain ends of UP prepolymers from several fundamental molecular parameters, including hydroxyl and carboxyl indexes, Ordelt saturation extent, short- and long-chain branch distribution, molecular polydispersity, and starting reactant composition and also reasonable assumptions concerning the chain-branch lengths. Simulation results were compared with experimental ones. The influences of the mentioned molecular parameters on the chain branches and on the overall molecular chain ends are discussed in this work. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 133–145, 1997

Centrifugal distortion effects for a molecule with two internal rotors

The centrifugal distortion effects for a molecule containing two symmetric internal rotors are formulated. The explicit expressions that relate the distortion constants to fundamental molecular parameters are given, which are applicable for analysing molecular structure from the parameters determined from a fit-to-observed spectrum or for calculating the centrifugal distortion constants from well known fundamental molecular parameters. The reduced torsion - rotation Hamiltonian is given for a molecule with two internal rotors with a symmetry plane which contains both internal rotation axes.

Higher-order effects in the vibration–torsion–rotation spectra of a molecule with an internal rotor

The sequential contact transformation technique is applied to the vibrational–torsional–rotational Hamiltonian for molecules containing a threefold symmetric internal rotor, which makes it possible to analyze various higher-order vibration–torsion–rotation interactions and their effects in the vibration–torsion–rotation spectra of the molecule. The formalism for the calculation of Hamiltonian coefficients is developed in terms of the fundamental molecular parameters. The resulting formulas are applicable to analyze the molecular structure. The theory presented is applied to the calculation of the quartic and sixtic centrifugal distortion constants of the molecule.

Crystallinity and dielectric properties of PEEK, poly(ether ether ketone)

The dependence of specific dielectric properties of polymers on their fundamental molecular parameters was investigated as part of a study involving HV insulation in spacecraft systems. As part of an effort to understand the causes of dielectric breakdown, this investigation focused on the effect of polymer morphology on the electrical characteristics of a poly (ether ether ketone) (PEEK), a high temperature insulating thermoplastic. Amorphous PEEK was thermally annealed to produce a range of crystallinities, and its dielectric properties were measured. As the crystalline/amorphous ratio of the polymer increased, the dielectric breakdown strength was reduced. The electrical conductivity of the material was also shown to decrease with increasing crystallinity. The effect on the permittivity was inconclusive.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Very low temperature spectroscopy: The pressure broadening coefficients for CO–He between 4.3 and 1.7 K

The attributes of very low temperature spectroscopy in the context of a simple collisionally cooled cell are described. Among them are narrow linewidths, large absorption coefficients, and the simplification of complex spectra. Most importantly, the technique makes possible the study of gas phase collisional processes under equilibrium conditions in a variable temperature environment below 4 K. In this regime the rotational energy level spacing is typically larger than kT, thereby both significantly simplifying the most exact theoretical calculations and giving a more direct link between experimental observables and fundamental molecular parameters. The results of a pressure broadening experiment in the CO–He system in the region between 4.24–1.78 K are described. It was found that the pressure broadening parameters varied from 21.3 to 40.0 MHz/Torr over this temperature region. Comparison with earlier theoretical calculations showed excellent agreement at the higher temperatures; however, at the lowest observed temperature the theoretical value was about 20% greater than the measurement.

Theory of elementary bimolecular reactions in liquid solutions. 2. Prediction of bimolecular reaction rates from fundamental molecular parameters

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTheory of elementary bimolecular reactions in liquid solutions. 2. Prediction of bimolecular reaction rates from fundamental molecular parametersA. J. BenesiCite this: J. Phys. Chem. 1984, 88, 20, 4729–4735Publication Date (Print):September 1, 1984Publication History Published online1 May 2002Published inissue 1 September 1984https://doi.org/10.1021/j150664a057RIGHTS & PERMISSIONSArticle Views55Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (869 KB) Get e-Alerts

Sextic centrifugal distortion constants of polyatomic molecules

Detailed expressions, in terms of fundamental molecular parameters, are given for the sextic centrifugal distortion constants for a general polyatomic molecule. The calculation of these expressions is based on the Watson molecular vibrational-rotational hamiltonian using third and fourth-order ordinary perturbation theory. Numerical examples are given for the H2S, SO2 and NH3 molecules. The calculated and observed sextic constants for these molecules are in good agreement.

Fourth-order centrifugal distortion coefficients for the nonlinear XYZ molecule

Detailed expressions in terms of fundamental molecular parameters are given for the ten fourth-order centrifugal distortion constants of the nonlinear XYZ molecule. The calculation of these coefficients is based on the Darling-Dennison Hamiltonian in the Nielsen-Amat-Goldsmith expansion.

A complete fourth-order vibration-rotation Hamiltonian for the bent XYX molecule

Detailed expressions in terms of the fundamental molecular parameters for all coefficients of the Hamiltonian of the bent XYX (H 2O type) molecule are given. The calculation of these coefficients is based on the Darling-Dennison Hamiltonian in the Amat-Nielsen-Goldsmith expansion.

Viscoelastic properties of amorphous polymers in the rubberlike elastic state as a function of the nature and length of the polymer chain

The effect of the fundamental molecular parameters on the behavior of polymers in the region of the rubberlike-elasticity plateau is analyzed to find “corresponding states” of different polymers and methods for reducing the experimental data to a generalized form.

Fourth-Order Vibration–Rotation Hamiltonian of the Nonlinear XYX Molecule

Detailed expressions in terms of fundamental molecular parameters are given for the fourth-order centrifugal distortion constants of the nonlinear XYX molecule. It is shown how these expressions can be used for the determination of the cubic potential constants of the XYX molecule if they are considered in conjunction with the reduced-Hamiltonian theory of Watson. Three reduced Hamiltonians are treated in detail, and a generalization of Watson's theory is presented, and its need is justified.