Systematic coarse-graining of potential energy landscapes and dynamics in liquids

Recent efforts have shown that the dynamic properties of a wide class of liquids can be mapped onto semi-universal scaling laws and constitutive relations that are motivated by thermodynamic analyses of much simpler models. In particular, it has been found that many systems exhibit dynamics whose behavior in state space closely follows that of soft-sphere particles interacting through an inverse power repulsion. In the present work, we show that a recently developed coarse-graining theory provides a natural way to understand how arbitrary liquids can be mapped onto effective soft-sphere models and hence how one might potentially be able to extract underlying dynamical scaling laws. The theory is based on the relative entropy, an information metric that quantifies how well a soft-sphere approximation to a liquid's multidimensional potential energy landscape performs. We show that optimization of the relative entropy not only enables one to extract effective soft-sphere potentials that suggest an inherent scaling of thermodynamic and dynamic properties in temperature-density space, but that also has rather interesting connections to excess entropy based theories of liquid dynamics. We apply the approach to a binary mixture of Lennard-Jones particles, and show that it gives effective soft-sphere scaling laws that well-describe the behavior of the diffusion constants. Our results suggest that the relative entropy formalism may be useful for "perturbative" type theories of dynamics, offering a general strategy for systematically connecting complex energy landscapes to simpler reference ones with better understood dynamic behavior.     

Traceability to units

On the grounds that clear and direct communication is required of us today, it is proposed that traceability be regarded as the ability to demonstrate that measurements are what they are purported to be and that traceability is thus to measurement units rather than reference values per se. It is suggested that such an approach may give greater flexibility in the establishment, maintenance and propagation of traceability, and that accreditation practices are becoming central to the practical establishment of traceability for chemical and biological measurement.     

The molecular origins of nonlinear response in solute energy relaxation: the example of high-energy rotational relaxation

A key step in solution-phase chemical reactions is often the removal of excess internal energy from the product. Yet, the way one typically studies this process is to follow the relaxation of a solute that has been excited into some distribution of excited states quite different from that produced by any reaction of interest. That the effects of these different excitations can frequently be ignored is a consequence of the near universality of linear-response behavior, the idea that relaxation dynamics is determined by the solvent fluctuations (which may not be all that different for different kinds of solute excitation). Nonetheless, there are some clear examples of linear-response breakdowns seen in solute relaxation, including a recent theoretical and experimental study of rapidly rotating diatomics in liquids. In this paper we use this rotational relaxation example to carry out a theoretical exploration of the conditions that lead to linear-response failure. Some features common to all of the linear-response breakdowns studied to date, including our example, are that the initial solute preparation is far from equilibrium, that the subsequent relaxation promotes a significant rearrangement of the liquid structure, and that the nonequilibrium response is nonstationary. However, we show that none of these phenomena is enough to guarantee a nonlinear response. One also needs a sufficient separation between the solute time scale and that of the solvent geometry evolution. We illustrate these points by demonstrating precisely how our relaxation rate is tied to our liquid-structural evolution, how we can quantitatively account for the initial nonstationarity of our effective rotational friction, and how one can tune our rotational relaxation into and out of linear response.     

Simulation studies of protein folding/unfolding equilibrium under polar and nonpolar confinement

We study the equilibrium folding/unfolding thermodynamics of a small globular miniprotein, the Trp cage, that is confined to the interior of a 2 nm radius fullerene ball. The interactions of the fullerene surface are changed from nonpolar to polar to mimic the interior of the GroEL/ES chaperonin that assists proteins to fold in vivo. We find that nonpolar confinement stabilizes the folded state of the protein due to the effects of volume reduction that destabilize the unfolded state and also due to interactions with the fullerene surface. For the Trp cage, polar confinement has a net destabilizing effect that results from the stabilizing confinement and the competitive exclusion effect that keeps the protein away from the surface hydration shell and stronger interactions between charged side chains in the protein and the polar surface that compete against the formation of an ion pair that stabilizes the protein folded state. We show that confinement effects due to volume reduction can be overcome by sequence-specific interactions of the protein side chains with the encapsulating surface. This study shows that there is a complex balance among many competing effects that determine the mechanism of GroEL chaperonin in enhancing the folding rate of polypeptide inside its cavity.     

Potential of mean force for tetramethylammonium binding to cagelike oligosilicates in aqueous solution

We have carried out free energy calculations to compute the potential of mean force for the cagelike silicate polyion-TMA+ cation ion pair interaction in aqueous solution. We also have studied solvent reorganization-related entropic effects. We conclude that the organocations, as opposed to, for example, alkali-metal ions, play a pivotal role in reorganizing the solvent around the cagelike silicates in a manner conducive to the formation of heteronetwork clathrates that are stable both thermodynamically and kinetically. In the case of stable cagelike polysilicate anions, this solvent reorganization correlates with entropic losses. We also infer that transient cagelike polysilicate species, that may indeed form but participate in floppy clathrates, eventually have to give way to cagelike polysilicates that lead to more rigid structures.     

Mass spectrometric characteristics and kinetics of iron release in visceral mass of Saccostrea cucullata

Ferritins with electrophoretic homogeneity were prepared from the visceral mass of Saccostrea cucullata in batch. The native PAGE approach showed similar electrophoretic mobility among pig pancreatic ferritin, liver ferritin of Dasyatis akajei, and visceral mass ferritin of Saccostrea cucullata. SDS-PAGE indicated that the Saccostrea cucullata visceral ferritin (SCVF) consisted of a single subunit type and had a molecular weight (MW) of approximately 20 kDa, suggesting that the protein shell in SCVF was composed of a single subunit. In addition, peptide mass fingerprinting and transmission electron microscopy were used to identify SCVF further, and to observe its molecular structure. We found that the molecular structure in SCVF was similar to that of most mammalian ferritins, which are composed of a protein shell and an iron core. The results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry under the assistance of an acidic matrix, sinapic acid, also showed that SCVF was composed of a single subunit type and its subunit MW was calculated to be 19871.042 Da in the absence of heme. Kinetics analysis revealed that the complete process of iron release fitted the law of a first-order reaction, which is similar to that of most ferritins in mammals. Similar to bacterial ferritin, studies indicated that the shell consisted of a single subunit type and showed similar kinetics of iron release, suggesting that this subunit plays two important roles in iron release and storage, and that it shows different stability and intensity of interaction in carrying out its physiological functions in SCVF.     

Prediction of retention times of proteins in hydrophobic interaction chromatography using only their amino acid composition

This paper focuses on the prediction of the dimensionless retention time of proteins (DRT) in hydrophobic interaction chromatography (HIC) by means of mathematical models based, essentially, only on aminoacidic composition. The results show that such prediction is indeed possible. Our main contribution was the design of models that predict the DRT using the minimal information concerning a protein: its aminoacidic composition. The performance is similar to that observed in models that use much more sophisticated information such as the three-dimensional structure of proteins. Three models that, in addition to the amino acid composition, use different assumptions about the amino acids tendency to be exposed to the solvent, were evaluated in 12 proteins with known experimental DRT. In all the cases analyzed, the model that obtained the best results was the one based on a linear estimation of the aminoacidic surface composition. The models were adjusted using a collection of 74 vectors of aminoacidic properties plus a set of 6388 vectors derived from these using two mathematical tools: k-means and self-organizing maps (SOM) algorithms. The best vector was generated by the SOM algorithm and was interpreted as a hydrophobicity scale based partly on the tendency of the amino acids to be hidden in proteins. The prediction error (MSE(JK)) obtained by this model was almost 35% smaller than that obtained by the model that supposes that all the amino acids are completely exposed and 40% smaller than that obtained by the model that uses a simple correction factor considering the general tendency of each amino acid to be exposed to the solvent. In fact, the performance of the best model based on the aminoacidic composition was 5% better than that observed in the model based on the three-dimensional structure of proteins.     

The Film Formation of Polymer Particles in Drying Thin Films of Aqueous Acrylic Latices

The aim of this study is to determine the factors that contribute to the process of film formation of binder particles in drying aqueous dispersion coatings, based on acrylic polymers. It is known that concentrated latices of uniform size show iridescent, colored light patterns. These colors are caused by interparticle interference, and they are only present when the latex particles are ordered in a regular structure. The interparticle interference can be characterized by measuring the transmission as a function of wavelength of the incident light. It appeared that the changes of the interparticle interference of a drying latex film can be related to changes in the interparticle distance and displacement. It was also found that the interparticle distance becomes "negative" upon coalescence of the latex particles. This means that from this point on, the change in interparticle interference is directly related to the indentation or deformation of the latex particles. It became clear that the coalescence process differs from deformation mechanisms accepted in the literature. It seems that the deformation of the particles follows a biaxial mechanism. This means that the particles deform only in one direction, perpendicular to the film surface. Copyright 2000 Academic Press.     

Non-invasive detection of superimposed latent fingerprints and inter-ridge trace evidence by infrared spectroscopic imaging

Current latent print and trace evidence collecting technologies are usually invasive and can be destructive to the original deposits. We describe a non-invasive vibrational spectroscopic approach that yields latent fingerprints that are overlaid on top of one another or that may contain trace evidence that needs to be distinguished from the print. Because of the variation in the chemical composition distribution within the fingerprint, we demonstrate that linear unmixing applied to the spectral content of the data can be used to provide images that reveal superimposed fingerprints. In addition, we demonstrate that the chemical composition of the trace evidence located in the region of the print can potentially be identified by its infrared spectrum. Thus, trace evidence found at a crime scene that previously could not be directly related to an individual, now has the potential to be directly related by its presence in the individual-identifying fingerprints. A portion of this work was presented at the 16th Meeting of the International Association of Forensic Sciences, Montpellier, France September 2–7, 2002.     

Modelling the voltammetry of adsorbed enzymes and molecular catalysts

When redox enzymes are attached to electrodes and undergo direct electron transfer, their voltammetric responses exhibit diverse shapes that, if analysed correctly, may inform about various aspects of the catalytic mechanism. Here we review the models that have been proposed to interpret these signals in relation to the thermodynamics and kinetics of interfacial and intramolecular electron transfer and active site chemistry. We list the corresponding equations in forms that are ready to use for fitting, and the commands that run these fits in the open source software QSoas. We relate these models to those that have been used for characterizing small synthetic redox catalysts diffusing in solution.     

A Shortcut Application of a Flory‐Like Model to Asphaltene Precipitation

A model, previously developed to determine the asphaltene precipitation onset, considered that asphaltene separation is ruled by the solvent quality of the surrounding media. Here, it is shown that it is equivalent to Flory‐Huggins model, when it is hypothesized that the asphaltene concentration is always in the instability range. With this, the controversy on the use of a concentration‐dependent model to describe a phenomenon that is practically independent of concentration is by‐passed. Moreover, improvements of the model are presented, together with sensitivity analysis with respect to its parameters. Two field case applications are reported, showing that the model gives a reasonable fit.     

The molecular underpinnings of a solute-pump/solvent-probe spectroscopy: the theory of polarizability response spectra and an application to preferential solvation

Recent ultrafast experiments on liquids have made clear that it is possible to go beyond light scattering techniques such as optical Kerr spectroscopy that look at the dynamics of a liquid as a whole. It is now possible to measure something far more conceptually manageable: how that liquid dynamics (and that light scattering) can be modified by electronically exciting a solute. Resonant-pump polarizability-response spectra (RP-PORS) in particular, seem to show that different solvents respond in noticeably distinct ways to such solute perturbations. This paper is a theoretical attempt at understanding the kinds of molecular information that can be revealed by experiments of this sort. After developing the general classical statistical mechanical linear response theory for these spectra, we show that the experimentally interesting limit of long solute-pump/solvent-probe delays corresponds to measuring the differences in 4-wave-mixing spectra between solutions with equilibrated ground- and excited-state solutes-meaning that the spectra are essentially probes of how changing liquid structure affects intermolecular liquid vibrations and librations. We examine the spectra in this limit for the special case of an atomic solute dissolved in an atomic-liquid mixture, a preferential solvation problem, and show that, as with the experimental spectra, different solvents can lead to spectra with different magnitudes and even different signs. Our molecular-level analysis of these results points out that solvents can also differ in how local a portion of the solvent dynamics is accessed by this spectroscopy.     

Systematic mutational analysis of an ubiquitin ligase (MDM2)-binding peptide: computational studies

To understand the importance of amino acids that comprise the peptide PMI (p53-MDM2/MDMX inhibitor), a p53-mimicking peptide with high affinity for the ubiquitin ligase MDM2, computational alanine scanning has been carried out using various protocols. This approach is very useful for identifying regions of a peptide that can be mutated to yield peptides that bind to their targets with higher affinities. Computational alanine scanning is a very useful technique that involves mutating each amino acid of the peptide in its complex with its target (MDM2 in the current study) to alanine, running short simulations on the mutated complex and computing the difference in interaction energies between the mutant peptides and the target protein (MDM2 in the current study) relative to the interaction energy of the original (wild-type) peptide and the target protein (MDM2 in the current study). We find that running multiple short simulations yield values of computed binding affinities (enthalpies) that are similar to those obtained from a long simulation and are well correlated with the trends in the data available from experiments that used Surface Plasmon Resonance to obtain dissociation constants. The p53-mimicking peptides contain three amino acids (F19, W23 and L26) that are major determinants of the interactions between the peptides and MDM2 and form an essential motif. We find in the current study that the trends amongst the contributions to experimental binding affinities of the hydrophobic residues F19, W23 and L26 are the best reproduced in all the computational protocols examined here. This study suggests that running such short simulations may provide a rapid method to redesign peptides to obtain high-affinity variants against a target protein. We further observe that modelling an extended conformation at the C-terminus of the helical PMI peptides, in accord with the conformation of the p53-peptide complexed to MDM2, reproduces the trends seen amongst the experimental affinities of the peptides that carry the alanine mutations at their C-termini. This suggests that some of the mutant peptides possibly interconvert between helical and extended states and can bind to MDM2 in either conformation. This novel feature, not obvious from the crystallographic data, if factored into modelling protocols, may yield novel high-affinity peptides. Our findings suggest that such protocols may enable rapid investigations of at least certain types of amino acid mutations, notably from large to small amino acids.     

温度对线性和交联聚酰亚胺摩擦磨损性能的影响

用栓 盘式磨损试验机考察了环境温度对线型（ＹＳ ２０）和交联（ＫＨ ３０４）聚酰亚胺摩擦磨损特性的影响．试验结果表明：在不同温度下，两种聚酰亚胺摩擦系数随滑动时间的变化，ＹＳ ２０是先增大，继而降低，最后趋于稳定；而ＫＨ ３０４是先降低，然后趋于稳定．对于摩擦系数的稳定值，随温度的升高，ＹＳ ２０呈先升高后下降的趋势，ＫＨ ３０４呈先降低后稳定的趋势．两者的磨损均随温度的升高而升高，在同一温度下，ＫＨ ３０４的磨损大于ＹＳ ２０．结合扫描电镜（ＳＥＭ）和傅立叶红外（ＦＴＩＲ）的观察分析，作者认为温度影响聚酰亚胺摩擦磨损性能的原因，对ＹＳ ２０主要为摩擦表面层物理状态发生了由玻璃态、高弹态到粘流态的变化，对ＫＨ ３０４则为摩擦表面层发生的化学变化     

5-Hydroxymethylcytosine, the sixth base of the genome

5-Hydroxymethylcytosine (hmC) was recently discovered as a new constituent of mammalian DNA. Besides 5-methylcytosine (mC), it is the only other modified base in higher organisms. The discovery is of enormous importance because it shows that the methylation of cytosines to imprint epigenetic information is not a final chemical step that leads to gene silencing but that further chemistry occurs at the methyl group that might have regulatory function. Recent progress in hmC detection--most notably LC-MS and glucosyltransferase assays--helped to decipher the precise distribution of hmC in the body. This led to the surprising finding that, in contrast to constant mC levels, the hmC levels are strongly tissue-specific. The highest values of hmC are found in the central nervous system. It was furthermore discovered that hmC is involved in regulating the pluripotency of stem cells and that it is connected to the processes of cellular development and carcinogenesis. Evidence is currently accumulating that hmC may not exclusively be an intermediate of an active demethylation process, but that it functions instead as an important epigenetic marker.     

Different crystal morphologies lead to slightly different conformations of light-harvesting complex II as monitored by variations of the intrinsic fluorescence lifetime

In 2005, it was found that the fluorescence of crystals of the major light-harvesting complex LHCII of green plants is significantly quenched when compared to the fluorescence of isolated LHCII (A. A. Pascal et al., Nature, 2005, 436, 134-137). The Raman spectrum of crystallized LHCII was also found to be different from that of isolated LHCII but very similar to that of aggregated LHCII, which has often been considered a good model system for studying nonphotochemical quenching (NPQ), the major protection mechanism of plants against photodamage in high light. It was proposed that in the crystal LHCII adopts a similar (quenching) conformation as during NPQ and indeed similar changes in the Raman spectrum were observed during NPQ in vivo (A. V. Ruban et al., Nature, 2007, 450, 575-579). We now compared the fluorescence of various types of crystals, differing in morphology and age. Each type gave rise to its own characteristic mono-exponential fluorescence lifetime, which was 5 to 10 times shorter than that of isolated LHCII. This indicates that fluorescence is not quenched by random impurities and packing defects (as proposed recently by T. Barros et al., EMBO Journal, 2009, 28, 298-306), but that LHCII adopts a particular structure in each crystal type, that leads to fluorescence quenching. Most interestingly, the extent of quenching appears to depend on the crystal morphology, indicating that also the crystal structure depends on this crystal morphology but at the moment no data are available to correlate the crystals' structural changes to changes in fluorescence lifetime.     

The natural product avrainvillamide binds to the oncoprotein nucleophosmin

Here we present evidence that (+)-avrainvillamide, a naturally occurring alkaloid with antiproliferative effects, binds to the nuclear chaperone nucleophosmin, a proposed oncogenic protein that is overexpressed in many different human tumors. Among other effects, nucleophosmin is known to regulate the tumor suppressor protein p53. A synthetic biotin-avrainvillamide conjugate, nearly equipotent to the natural product in inhibiting the growth of cultured T-47D cells, was used for affinity-isolation of a protein identified as nucleophosmin by MS sequencing and Western-blotting. Affinity-isolation of nucleophosmin was inhibited in the presence of iodoacetamide (10 mM), free (+)-avrainvillamide (100 microM), and a series of closely related structural analogues of (+)-avrainvillamide, the latter with inhibitory effects that appear to correlate with measured growth-inhibitory potencies. Using fluorescence microscopy, a synthetic dansyl-avrainvillamide conjugate was observed to localize within the nucleoli and the cytosol of treated cancer cells. Site-directed mutagenesis of each of the three cysteine residues of a truncated nucleophosmin coexpressed with native nucleophosmin in COS-7 cells revealed that the mutation cys275 --> ala275 effectively and uniquely reduced affinity-isolation of the truncated protein, suggesting that avrainvillamide targets cys275 of nucleophosmin. Finally, we show that treatment of adhered LNCaP or T-47D cells with (+)-avrainvillamide leads to an increase in cellular p53 concentrations, and that siRNA-promoted depletion of nucleophosmin in a population of HeLa S3 cells leads to increased sensitivity of that population toward apoptotic death upon treatment with (+)-avrainvillamide. Although potentially desirable as lead compounds for the development of novel anticancer therapies, nonpeptidic, synthetic small molecules that bind to nucleophosmin have not been described, prior to this report.     

The International System of Units��a case for reconsideration

The International System of Units (SI) follows a concept that goes back to Maxwell. At that time, a logic sound foundation of mathematics was not yet available. This has lead to concepts and terms that are contradictory and in conflict with today??s standard mathematical concepts. The inconsistencies that have evolved in metrology due to the lack of appropriate notions are pointed out. This is most important, as the metrology is a field that is internationally well organized under the umbrella of the Meter Convention, an international treaty for acting on all matters relating to units of measurement. Committees and working groups under the Meter Convention have a leading role in the elaboration of important metrological guides, among others the International Vocabulary of Metrology. Therefore, it is highly desirable that their publications use well-founded concepts and terminology. It is consensus that it is desirable to find a system of units on invariant properties of nature and not on human artifacts, e.g., the prototype of the kilogram. However, the current proposals to improve that are in conflict with standard scientific concepts. It is shown in the paper how these inconsistencies can be avoided. The argumentation is based on the interpretation of numbers developed by mathematicians like Cantor, Dedekind, Peano, and others that have led the logic foundation of mathematics with set and number theory. This foundation excludes dogmas that have been forwarded in the last century under the umbrella of the Meter Convention.     

Influence of the length and position of the collision cell on the resolving power attainable from collisionally activated processes in sector instruments

The energy resolution in a high resolution tandem mass spectrometer was investigated in terms of the length and position of the central collision cell. Both these parameters have to be chosen carefully to eliminate collisional broadening phenomena that can severely limit the energy resolution in such instruments. A theory that describes collisional broadening, to first order, has been derived that accounts for the observed phenomena. It was found experimentally that collisional broadening can be reduced to less than 0.001 eV per kiloelectronvolt collision energy. Experimental data confirmed that only the size of the resolving slits and thermal broadening, due to the target gas, limited the ultimate energy resolution available.     

Air oxidation of hydrazine. 1. Reaction kinetics on natural kaolinites, halloysites, and model substituent layers with varying iron and titanium oxide and O- center contents

Air oxidation of hydrazine was studied by using a group of kaolinites, halloysites, and substituent oxides as models for the tetrahedral and octahedral sheets. The rate was found to be linear with oxygen. The stoichiometry showed that oxygen was the primary oxidant and that dinitrogen was the only important nitrogen-containing product. The rates on kaolinites were strongly inhibited by water. Those on three-dimensional silica and gibbsite appeared not to be. That on a supposedly layered silica formed from a natural kaolinite by acid leaching showed transitional behavior--slowed relative to that expected from a second-order reaction relative to that on the gibbsite and silica but faster than those on the kaolinites. The most striking result of the reaction was the marked increase in the rate of reaction of a constant amount of hydrazine as the amount of clay was increased. The increase was apparent (in spite of the water inhibition at high conversions) over a 2 order of magnitude variation of the clay weight. The weight dependence was taken to indicate that the role of the clay is very important, that the number of reactive centers is very small, or that they may be deactivated over the course of the reaction. In contrast to the strong dependence on overall amount of clay, the variation of amounts of putative oxidizing centers, such as structural Fe(III), admixed TiO2 or Fe2O3, or O- centers, did not result in alteration of the rate commensurate with the degree of variation of the entity in question. Surface iron does play some role, however, as samples that were pretreated with a reducing agent were less active as catalysts than the parent material. These results were taken to indicate either that the various centers interact to such a degree that they cannot be considered independently or that the reaction might proceed by way of surface complexation, rather than single electron transfers.