Intricate packing in the hydrophobic core of barstar through a CH–π interaction

Identification of specific packing interactions within in the hydrophobic core of proteins is important for understanding the integrity of protein structure. Finding such interactions is challenging because few tools allow monitoring of a specific interaction in the presence of several non‐specific forces that hold proteins together. It is important to understand how and when such interactions develop during protein folding. In this study, we have used the intrinsic tryptophan residue, Trp53, as an ultraviolet resonance Raman probe to elucidate the packing interactions in the hydrophobic core of the protein barstar. Barstar is extensively studied for its folding, unfolding and aggregation properties. The Trp53 residue is known to be completely buried in the hydrophobic core of the protein and is used extensively as an intrinsic probe to monitor the folding and unfolding reactions of barstar. A comparison of the resonance Raman cross sections of some bands of Trp53 with those observed for N‐acetyl‐tryptophanoamide in water suggests that Trp53 in barstar is indeed isolated from water. Intensity ratio of the Fermi doublet suggests that Trp53 is surrounded by several aliphatic amino acid residues in corroboration with the crystal structure of barstar. Importantly, we show that the side chain of Trp53 is involved in a unique CH–π interaction with CH groups of Phe56 as well as a steric interaction with the methyl group of Ile5. Copyright © 2014 John Wiley & Sons, Ltd.     

Hydrophobic and Ionic-Interactions in Bulk and Confined Water with Implications for Collapse and Folding of Proteins

Water and water-mediated interactions determine the thermodynamics and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano-sized water droplets. Solvation of hydrophobic and charged species change drastically in nano-scale water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. The interactions between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores.     

A study of Barstar folding events using boundary value simulations

From extensive biophysical studies of protein folding, two competing mechanisms emerged: hydrophobic collapse and the framework model. Our protein of choice is Barstar—a barnase inhibitor. The approximation algorithm we used to study Barstar folding trajectories is called SDEL—stochastic difference equation in length. Using the native structure as the final boundary value and a collection of unfolded structures as the varying initial boundary value, SDEL calculates an ensemble of least action pathways between these boundaries. The results are atomically detailed folding pathways, with as many intermediate structures as you request in the input. We generated 12 pathways, starting from a structurally wide selection of unfolded conformations. Using the protein's radius of gyration as our primary reaction coordinate, we tracked H-bonds, dihedral angles, native and non-native contacts, and energy along the folding pathways. This paper will follow our findings, with special emphasis on pinpointing hydrophobic collapse as a more appropriate mechanism for Barstar. Comparison with pathway predictions for Barstar using experimental techniques will also be discussed.     

Molecular Mechanism of the Early Stage of Amyloidogenic Hexapeptides (NFGAIL) Aggregation

Peptides/proteins aggregation can give rise to pathological conditions of many human diseases. Small partially ordered oligomers formed in the early stage of aggregation, rather than mature fibrils, are thought to be the main toxicity agent for the living cell. Thus, understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases. Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides (NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide). We observe that the peptide monomers in water mainly adopt non-structural coil configurations; the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer (β-sheets) through dimerization or trimerization, with the dimerization predominated. Both parallel and anti-parallel β-sheets are observed. The hydrophobic interactions drive the initial peptides associations, and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides.     

Sensing Tryptophan Microenvironment of Amyloid Protein Utilizing Wavelength-Selective Fluorescence Approach

Structural transition among various forms of proteins involves subtle interplay between structure and dynamics and is crucial in human diseases. Red edge excitation shift (REES) represents a suitable approach to explore the environmental organization and dynamics surrounding tryptophan residues in proteins. Although REES from tryptophan residues has been reported for native, molten globule and denatured states of proteins, such data on the amyloid form of proteins is lacking. κ-casein is one of the most important constituents of casein micelles in milk and has a tendency to form amyloid fibril. We report here REES of the sole tryptophan residue for native, acid-denatured and urea-denatured forms of κ-casein. More importantly, we show that the amyloid form of κ-casein displays REES of 4 nm. We analyze these results in terms of tryptophan microenvironment in various forms of κ-casein, particularly the amyloid form. We conclude that REES is a sensitive tool to monitor structural plasticity in proteins.     

Infrared studies of the role of monoclinic structure in the deformation of polyethylene

The transformation from the orthorhombic to the monoclinic structure has been observed by means of infrared spectroscopy in shaken preparations of single crystals of polyethylene, mixed crystals of polyethylene and perdeuteropolyethylene, and physical mixtures of single crystals of these two polymers. Annealing of such shaken samples results in the conversion of the monoclinic back to the orthorhombic structure, but with an accompanying change from the (110) folding characteristic of single crystals to (200) folding. The monoclinic structure thus appears to be an intermediate state in the fold-plane transformation which can occur upon deformation. Both unannealed and annealed physical mixtures give evidence of ciliary penetration.     

Permutation Entropy-Based Interpretability of Convolutional Neural Network Models for Interictal EEG Discrimination of Subjects with Epileptic Seizures vs. Psychogenic Non-Epileptic Seizures

The differential diagnosis of epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) may be difficult, due to the lack of distinctive clinical features. The interictal electroencephalographic (EEG) signal may also be normal in patients with ES. Innovative diagnostic tools that exploit non-linear EEG analysis and deep learning (DL) could provide important support to physicians for clinical diagnosis. In this work, 18 patients with new-onset ES (12 males, 6 females) and 18 patients with video-recorded PNES (2 males, 16 females) with normal interictal EEG at visual inspection were enrolled. None of them was taking psychotropic drugs. A convolutional neural network (CNN) scheme using DL classification was designed to classify the two categories of subjects (ES vs. PNES). The proposed architecture performs an EEG time-frequency transformation and a classification step with a CNN. The CNN was able to classify the EEG recordings of subjects with ES vs. subjects with PNES with 94.4% accuracy. CNN provided high performance in the assigned binary classification when compared to standard learning algorithms (multi-layer perceptron, support vector machine, linear discriminant analysis and quadratic discriminant analysis). In order to interpret how the CNN achieved this performance, information theoretical analysis was carried out. Specifically, the permutation entropy (PE) of the feature maps was evaluated and compared in the two classes. The achieved results, although preliminary, encourage the use of these innovative techniques to support neurologists in early diagnoses.     

Measuring thermodynamic length

Thermodynamic length is a metric distance between equilibrium thermodynamic states. Among other interesting properties, this metric asymptotically bounds the dissipation induced by a finite time transformation of a thermodynamic system. It is also connected to the Jensen-Shannon divergence, Fisher information, and Rao's entropy differential metric. Therefore, thermodynamic length is of central interest in understanding matter out of equilibrium. In this Letter, we will consider how to define thermodynamic length for a small system described by equilibrium statistical mechanics and how to measure thermodynamic length within a computer simulation. Surprisingly, Bennett's classic acceptance ratio method for measuring free energy differences also measures thermodynamic length.     

Self-organized critical model for protein folding

The major factor that drives a protein toward collapse and folding is the hydrophobic effect. At the folding process a hydrophobic core is shielded by the solvent-accessible surface area of the protein. We study the fractal behavior of 5526 protein structures present in the Brookhaven Protein Data Bank. Power laws of protein mass, volume and solvent-accessible surface area are measured independently. The present findings indicate that self-organized criticality is an alternative explanation for the protein folding. Also we note that the protein packing is an independent and constant value because the self-similar behavior of the volumes and protein masses have the same fractal dimension. This power law guarantees that a protein is a complex system. From the analyzed data, q-Gaussian distributions seem to fit well this class of systems.     

Analysis of time-resolved XANES spectra for determining the organometallic compound structure in solution

A method for analyzing time-resolved X-ray absorption spectra is proposed, which allows for the determination of the local structure of intermediate forms of organometallic compounds during reactions and the time dependence of their concentrations. The approach is based on the principal component analysis of a series of experimental spectra, which makes it possible to extract the spectra of intermediate products from the superposition of the initial, final, and all intermediate components. This stage also allows for the determination of the number of intermediate states. In the second stage, the parameters of the local structure are determined by minimizing the difference between theoretical and extracted (from the experiment) spectra of the intermediate compound forms. The theoretical spectra are calculated using a multidimensional interpolation of the XANES spectra for models with several varied structural parameters. The proposed scheme was tested on numerically generated data for the activation reaction of nickel isocyanide during the polymerization reaction.     

Hydrophobic/hydrophilic solvation: inferences from Monte Carlo simulations and experiments

In this study Monte Carlo simulations are used to determine the solvation properties of model hydrophobic (xenon and hard sphere) and hydrophilic (dimethyl ether) solutes in SPC/E water. Various contributions to the experimental solvation entropy, including the solvent reorganization entropy, have been determined. The main conclusion drawn, which is in accord with solubility data, is that poor solubility correlates with poor solute-water interaction. At room temperature, energy dominates the aqueous solubility of both hydrophobic and hydrophilic solutes, rather than entropy. However, at higher temperatures the solubility can pass through a minimum, and then entropy becomes dominant. Another interesting finding is the presence of larger than expected cavities in water. Two different simulation results support this finding. This unexpected hollow structure in water explains why a hard sphere solute is more soluble in water than in a comparable hard sphere or Lennard-Jones solvent. Hydrogen bonding causes water to aggregate into clusters that produce a few large cavities rather than many smaller cavities. The propensity for clustering also explains why water gives the illusion of being a low density liquid. Sufficient theoretical apparatus is developed to connect theoretical solvation properties to those measured by simulation and experiment. Finally, based on gas solubility, an intuitive hydrophobic/hydrophilic scale is developed.     

Real-space visualization of intercalated water phases at the hydrophobic graphene interface with atomic force microscopy

The phase behavior of water is a topic of perpetual interest due to its reinai kable anomalous properties and importance to biology,material science,geoscience,nanoscience,etc.It is predicted confined water at interface can exist in large amounts of crystalline or amorphous states.However,the experimental evidence of coexistence of liquid water phases at interface is still insufficient.Here,a special folding few-layers graphene film was elaborate prepared to form a hydrophobic/hydrophobic interface,which can provide a suited platform to study the structure and properties of confined liquid water.The real-space visualization of intercalated water layers phases at the folding interface is obtained using advanced atomic force microscopy(AFM).The folding graphene interface displays complicated internal interfacial characteristics.The intercalated water molecules present themselves as two phases,low-density liquid(LDL,solid-like)and high-density liquid(HDL,liquid-like),according to their specific mechanical properties taken in two multifrequency-AFM(MF-AFM)modes.Furthermore,the water molecules structural evolution is demonstrated in a series of continuous MF-AFM measurements.The work preliminary confirms the existence of two liquid phases of water in real space and will inspire further experimental work to deeply understanding their liquid dynamics behavior.     

Aggregation Behaviour of Cationic Diblock Copolymer （MTAC）10（BA）16： MesoDyn Simulation Study

The aggregation behaviour of an amphiphilic cationic block copolymer （MTAC）10（BA）16 in aqueous solution is investigated by MesoDyn simulation. Simulation results show that （MTAC）10 （BA）16 can form spherical, irregular and network aggregates with the increasing volume fraction. The time evolution of order parameter shows that the process of aggregate formation can be divided into diffusion control stage and hydrophobic interaction control stage, while the time evolution of energy indicates that the aggregate formation is driven by enthalpy but not entropy. The order parameter of the hydrophobic blocks BA increases with the increasing （MTAC）10（BA）16 concentration, while the time needed for system balance has the contrary trend.     

Vibrational entropy of dislocations in Al

The region nearest to a lattice defect must be described by an atomistic model, while a continuum model suffices further away from the defect. We study such a separation into two regions for an edge dislocation. In particular we focus on the excess defect energy and vibrational entropy, when the dislocation core is described by a cluster of about 500–100?atoms, embedded in a large discrete and relaxed, but static, lattice. The interaction between the atoms is given by a potential of the embedded-atom model type referring to Al. The dynamic matrix of the vibrations in the cluster is fully diagonalized. The excess entropy ΔS near the core has positive and negative contributions, depending on the sign of the local strain. Typically, ΔS/k _B ≈ 2 per atomic repeat length along the dislocation core in fcc Al. In the elastic continuum region far from the dislocation core the excess entropy shows the same logarithmic divergence as the elastic energy. Although the work refers to a specific material and defect type, the results are of a generic nature.     

How the liquid-liquid transition affects hydrophobic hydration in deeply supercooled water

We determine the phase diagram of liquid supercooled water by extensive computer simulations using the TIP5P-E model. We find that the transformation of water into a low density liquid in the supercooled range strongly enhances the solubility of hydrophobic particles. The transformation of water into a tetrahedrally structured liquid is accompanied by a minimum in the hydration entropy and enthalpy. The corresponding change in sign of the solvation heat capacity indicates a loss of one characteristic signature of hydrophobic hydration. The observed behavior is found to be qualitatively in accordance with the predictions of the information theory model of Garde et al.     

荧光光谱法研究盐酸胍浓度不同时变性胰蛋白酶的构象变化

蛋白变性过程中间体的存在是蛋白变性及复性动力学研究中不可缺少的证据。以胰蛋白酶为模型蛋白 ,用荧光光谱法系统地研究了在不同浓度变性剂盐酸胍存在时胰蛋白酶构象的变化 ,并与活性数据进行了对比。发现胰蛋白酶荧光光谱发射波长随变性剂盐酸胍浓度增大而逐渐增大 ,并且当盐酸胍浓度达到 2mol·L- 1 时胰蛋白酶的最大发射波长达到最大值 ,其后随盐酸胍浓度的增大最大发射波长反而逐渐减小 ,当盐酸胍浓度大于 3mol·L- 1 呈现不变的趋势。也就是说 ,在低浓度变性剂环境下 ,胰蛋白酶存在着一个与天然态和完全变性态的分子构象都不同的中间体状态 ,这个中间体状态的荧光发射波长最大 ,荧光发射强度也最大 ,而以此状态为复性起点 ,最终得到的复性产率也最低。对此原因从分子结构的基础上进行了探讨。     

Full Causal Theory of Bulk Viscosity and Specific Entropy of the Universe

This article deals with the full Israel–Stewart causal theory of bulk viscosity as employed to the dissipative expansion of the early universe. It is shown that the nontruncated full theory can be cast in the form of a noncausal theory with an auxiliary condition which states that the square of dissipative contribution to the speed of sound varies with the particle number in a comoving volume. Also, a generalized temperature appears in a cosmological invariant which is shown to hold good for the dissipative expansion in an intermediate brief transition period (around the epoch time = 10^–23 s) between the very early mild inflation stage of the universe and the standard radiation-dominated FRW era of it. With this generalized temperature, the Gibbs equation has been generalized. This equation is also shown to have an alternative form with a term depending on bulk viscosity. In the dissipative transition period, the universe as a thermodynamically open system of viscous fluid can generate specific entropy. In this period the temperature rose to a considerable extent. Due to the cosmological invariant, the dissipative contribution to the speed of sound and consequently the particle number decreased sharply, ensuring the second law of thermodynamics. It is possible to have an estimate of the specific entropy in consistency with the observations. The total entropy and the particle number of the observable universe have also been found here. These estimates agree with the accepted values for them.     

II. The intermediate velocity source in the 40Ca + 40Ca reaction at Elab = 35AMeV

The shape of the velocity distributions of charged particles projected on the beam direction can be explained if emissions from the hot projectile-like fragment and the target-like fragment are supplemented by an emission from an intermediate velocity source located between them. The creation of this source is predicted by a two-stage reaction model where, in the second stage, some of the nucleons identified in the first stage as participants form a group of clusters located in the region between the colliding nuclei. The cluster coalescence process is governed on the average by the maximum value of entropy, although its fluctuations are also significant. The properties of the intermediate velocity source are precisely described, including the isotopic composition of the emitted particles. Received: 12 March 2001 / Accepted: 20 June 2001     

Quantum Statistical Entropy of Dielectric Black Hole

Using the new equation of state density from the generalized uncertainty principle in quantum gravity, we study statistical entropy of a dielectric black hole. When λ introduced in the generalized uncertainty principle takes a specific value, we find that the leading term of the statistical entropy of the dielectric black hole takes the Bekenstein-Hawking entropy form. In addition a finite correction term is also obtained. Comparing with the original brick-wall model, in our calculation there is no divergence and the small mass approximation is also not needed.     

The role of hydrophobic interaction in phase transition and structure formation of lipid membranes and proteins

The hydrophobic interaction arises from the ordered structure of water around nonpolar groups of molecules in an aqueous solvent. Because biological systems are made of various macromolecules and amphiphiles which are suspended in aqueous solution, the hydrophobic interaction plays a very important role in the formation of higher-order structure and phase transitions in biological systems. Considering the hydrophobic interaction, the van der Waals interaction and the entropic effect, an equation of state of a lipid membrane was obtained which was analogous to the van der Waals equation. The characteristics of the lipid bilayer phase transition as well as the phase behaviors of a lipid monolayer were explained by this equation of state. Experimental evidence was obtained from ultrasonic measurements which indicated that its phase transition accompanys significant critical phenomena. Analysis of the hydrophobicity of amino acid sequences revealed that the morphology of the proteins was determined by the hydrophobicity alone. The essential role of the hydrophobic interaction in the morphogenesis of proteins could be confirmed by a denaturation experiment on a soluble protein, carbonic anhydrase B. Fluorescence measurements showed that an intermediate state, the so-called molten globule state, had a quite hydrophobic core, indicating that the globule shape of this protein is stabilized by the hydrophobic interaction.