Free Energy Profile and Mechanism of Self-Assembly of Peptide Amphiphiles Based on a Collective Assembly Coordinate

By combining targeted molecular dynamics (TMD) simulations, umbrella sampling, and the weighted histogram analysis method (WHAM), we have calculated the potential of mean force (PMF) for the transition between the bound and free states of 90 peptide amphiphiles (PAs) in aqueous solution, with the bound state corresponding to a cylindrical micelle fiber. We specifically consider a collective reaction coordinate, the radius of gyration of the PAs, to describe assembly in this work. It is found that the free energy, enthalpy, and entropy differences between the free and bound states are −126 kcal/mol, −185 kcal/mol, and −190 cal/(mol K), respectively, for the self-assembly process. This indicates that the driving force to form the micelle structure is enthalpic. The enthalpic driving forces originate from several factors, including the conformational energy of PAs and the electrostatic and van der Waals interaction energy between solvent molecules and between solvent and PAs. Among these interactions, the solvent electrostatic interaction is the dominating one, contributing 54% of the total driving force. The PMF profile can be recognized as involving two stages of assembly: (1) PAs initially approach each other in mostly random configurations and loosely aggregate, resulting in significant desolvation and initiation of head–tail conformational reorganization; (2) PAs undergo a conformational disorder-to-order transition, including forming secondary structures that include more β-sheets and fewer random coils, along with tail–head core–shell alignment and condensation that leads to total exclusion of water from the core. The PMF decreases slowly in the first stage, but rapidly in the second. This study demonstrates a hierarchy of assembly steps in which PA structural changes, solvation, and redistribution of solvent molecules play significant roles in the PA self-assembly process

Free-Energy Landscape for Peptide Amphiphile Self-Assembly: Stepwise versus Continuous Assembly Mechanisms

The mechanism of self-assembly of 140 peptide amphiphiles (PAs) to give nanofiber structures was investigated using a coarse-grained method to quantitatively determine whether the assembly process involves discrete intermediates or is a continuous process. Two novel concepts are introduced for this analysis, a cluster analysis of the time dependence of PA assembly and use of the fraction of native contacts as reaction coordinates for characterizing thermodynamic functions during assembly. The cluster analysis of the assembly kinetics demonstrates that a pillar-like intermediate state is formed before the final cylindrical semifiber structure. We also find that head group assembly occurs on a much shorter time scale than tail group assembly. A 2D free-energy landscape with respect to the fraction of native contacts was calculated, and the pillar-like intermediate structure was also found, with free energies about 1.2 kcal/mol higher than the final state. Although this intermediate state exists for only hundreds of nanoseconds, the PA self-assembly process can be recognized as involving two steps, (a) transition from the disordered state to the noncylindrical pillar-like intermediate and (b) pillar-like to final semifiber transition. These results are important to the further design of PAs as functional nanostructures

The effect of perceived global stress and altruism on prosocial driving behavior, yielding behavior, and yielding attitude

Traffic accidents are mainly caused by driver-to-pedestrian collisions or driver-to-driver collisions. Prosocial driving behavior indicates that drivers exhibit altruistic behavior toward other drivers on roads. Yielding behavior demonstrates that drivers grant the right of passage to pedestrians at unsignalized crossings, while yielding attitude presents the subjective emotional and cognitive inclination to yield to pedestrians at unsignalized crossings. This study aims to explore the effect of altruism and drivers’ perceived stress on prosocial driving behavior, yielding behavior, and yielding attitude. In addition, we endeavor to explore the effect of stress on prosocial driving behavior exhibiting an inverted “U-type” curve as Yerkes-Dodson’s law suggests and test the moderating role of perceived stress on altruism and prosocial driving behavior/yielding behavior/yielding attitude. Using a survey method, we asked 454 participants to complete an altruism scale from the IPIT measuring altruism, a Perceived Stress Scale-10 measuring drivers’ perceived stress, a prosocial driving scale from the PADI measuring prosocial driving behavior, and items on yielding behavior and yielding attitude. Then, a correlational matrix, a hierarchical multiple nonparametric regression analysis, and a moderating analysis of perceived stress were employed in sequence to reach our objective. The hierarchical multiple nonparametric regression analysis showed that altruism positively predicts yielding attitude (F = 41.56, p z = 8.46, p F = 110.66, p F = 7.63, p F = 0.51, p > 0.05) or yielding behavior (z = 0.12, p > 0.05), which exhibits an inverted “U-type” curve. Moderating analyses showed that stress only moderates the relationship between altruism and yielding attitude (B = −0.24, t = −2.62, p  Altruism is positively related to prosocial driving behavior, yielding behavior, and yielding attitude. Stress influences prosocial driving behavior only and exhibits an inverted “U-type” curve. Stress does not directly influence the yielding behavior. Instead, stress moderates the relationship between altruism and yielding attitude only and may further increase the possibility of yielding behavior.</p

Kinetic Study of Ozone Photocatalytic Decomposition Using a Thin Film of TiO₂ Coated on a Glass Plate and the CFD Modeling Approach

The kinetics of ozone photocatalytic decomposition in a flow-through reactor using a thin film of TiO₂ coated on a glass plate is investigated. The Langmuir–Hinshelwood kinetic model provides a good description of the ozone decomposition. The effect of light intensity on reaction rate is also studied, showing a transition in the kinetic order with respect to light intensity occurred from 0.75 to 1.0 mW·cm^–2 under the experimental conditions. Fluid dynamics and surface photocatalytic reaction modeling by the computational fluid dynamic (CFD) approach is then proposed. The parameters determined in the kinetic experiment are used to calculate the ozone concentration distribution in the flow-through reactor under a given radiation field. In terms of conversion yield, the model predictions agree closely with the experimental results within the range in which the results are examined. This study presents a simple example of the photocatalytic reaction process modeling. Knowledge of the intrinsic kinetics allows the universal application of this CFD approach to the optimization and design of photocatalytic reactors

Visualization 1: Development of a beam optimization method for absorption-based tomography

Evolution of the beam arrangement and the corresponding reconstruction from ART Originally published in Optics Express on 20 March 2017 (oe-25-6-5982

Molecular Dynamics Simulations and Electronic Excited State Properties of a Self-Assembled Peptide Amphiphile Nanofiber with Metalloporphyrin Arrays

We have employed molecular dynamics simulations and quantum chemistry methods to study the structures and electronic absorption properties of a novel type of photonic nanowire gel constructed by the self-assembly of peptide amphiphiles (PAs) and the chromophore-(PPIX)Zn molecules. Using molecular dynamics simulations, structures of the self-assembled fiber were determined with atomistic detail, including the distribution of chromophores along the nanofiber and the relative distances and orientations of pairs of chromophores. In addition, quantum chemistry calculations were used to determine the electronic structure and absorption properties of the chromophores in the fiber, so as to assess the capabilities of the nanofiber for photonics applications. The calculations show that the PA nanofiber provides an effective scaffold for the chromophores in which the chromophores form several clusters in which nearest neighbor chromophores are separated by less than 20 Å. The calculations also indicate that the chromophores can be in both the hydrophilic shell and hydrophobic core portions of the fiber. There are only small spectral shifts to the B-band of the porphyrins arising from the inhomogeneous microelectronic environment provided by the fiber. However, there are much stronger electronic interactions between nearby pairs of chromophores, leading to a more significant red shift of the B-band that is similar to what is found in the experiments and to significant excitonic coupling that is seen in circular dichroism spectra. This electronic interaction between chromophores associated with the PA nanofiber structure is crucial to future applications of these fibers for light-harvesting applications

Computational Insights into Five- versus Six-Coordinate Iron Center in Ferrous Soybean Lipoxygenase

Soybean lipoxygenase (SLO) serves as a prototype for fundamental understanding of hydrogen tunneling in enzymes. Its reactivity depends on the active site structure around a mononuclear, nonheme iron center. The available crystal structures indicate five-coordinate iron, while magnetic circular dichroism experiments suggest significant populations of both five-coordinate (5C) and six-coordinate (6C) iron in ferrous SLO. Quantum mechanical calculations of gas phase models produce only 6C geometries. Herein mixed quantum mechanical/molecular mechanical (QM/MM) calculations are employed to identify and characterize the 5C and 6C geometries. These calculations highlight the importance of the protein environment, particularly two Gln residues in a hydrogen-bonding network with Asn694, the ligand that can dissociate. This hydrogen-bonding network is similar in both geometries, but twisting of a dihedral angle in Asn694 moves its oxygen away from the iron in the 5C geometry. These insights are important for future simulations of SLO

Cardiomyocytes content of malondialdehyde (MDA) and superoxide dismutase (SOD) in sham-operated rats (Sham) and hypertension-induced left ventricular hypertrophy (H-LVH) rats treated with 5% glucose injection (GS) or tanshinone IIA (Tan) was observed (N = 8 per group).

<p>(A) MDA contents in rats cultured cardiomyocytes; (B) SOD activities in rats cultured cardiomyocytes.^#P<0.05 compared with sham group. *P<0.05 compared with 5%GS group.</p

Using a Monotonic Density Ratio Model to Find the Asymptotically Optimal Combination of Multiple Diagnostic Tests

<p>With the advent of new technology, new biomarker studies have become essential in cancer research. To achieve optimal sensitivity and specificity, one needs to combine different diagnostic tests. The celebrated Neyman–Pearson lemma enables us to use the density ratio to optimally combine different diagnostic tests. In this article, we propose a semiparametric model by directly modeling the density ratio between the diseased and nondiseased population as an unspecified monotonic nondecreasing function of a linear or nonlinear combination of multiple diagnostic tests. This method is appealing in that it is not necessary to assume separate models for the diseased and nondiseased populations. Further, the proposed method provides an asymptotically optimal way to combine multiple test results. We use a pool-adjacent-violation-algorithm to find the semiparametric maximum likelihood estimate of the receiver operating characteristic (ROC) curve. Using modern empirical process theory we show cubic root <i>n</i> consistency for the ROC curve and the underlying Euclidean parameter estimation. Extensive simulations show that the proposed method outperforms its competitors. We apply the method to two real-data applications. Supplementary materials for this article are available online.</p

Visualisation and Identification of the Interaction between STIM1s in Resting Cells

<div><p>Store-operated Ca²⁺ channels are a major Ca²⁺ entry pathway in nonexcitable cells, which drive various essential cellular functions. Recently, STIM1 and Orai proteins have been identified as the major molecular components of the Ca²⁺ release-activated Ca²⁺ (CRAC) channel. As the key subunit of the CRAC channel, STIM1 is the ER Ca²⁺ sensor and is essential for the recruitment and activation of Orai1. However, the mechanisms in transmission of information of STIM1 to Orai1 still need further investigation. Bimolecular fluorescence complementation (BiFC) is one of the most advanced and powerful tools for studying and visualising protein-protein interactions in living cells. We utilised BiFC and acceptor photobleaching fluorescence resonance energy transfer (FRET) experiments to visualise and determine the state of STIM1 in the living cells in resting state. Our results demonstrate that STIM1 exists in an oligomeric form in resting cells and that rather than the SAM motif, it is the C-terminus (residues 233–474) of STIM1 that is the key domain for the interaction between STIM1s. The STIM1 oligomers (BiFC-STIM1) and wild-type STIM1 colocalised and had a fibrillar distribution in resting conditions. Depletion of ER Ca²⁺ stores induced BiFC-STIM1 distribution to become punctate, an effect that could be prevented or reversed by 2-APB. After depletion of the Ca²⁺ stores, BiFC-STIM1 has the ability to form puncta that colocalise with wild-type STIM1 or Orai1 near the plasma membrane. Our data also indicate that the function of BiFC-STIM1 was not altered compared with that of wild-type STIM1.</p> </div