Conformational Order Research Articles

Structure – Bioactivity Relationship in Cyclic Peptoids: An Overview

AbstractCyclic N‐substituted glycines oligomers, also known as cyclic peptoids, constitute a promising class of novel peptidomimetics, capable of simulating bioactive effectors with enhanced proteolytical stability and cell permeability as crucial bonuses. The macrocyclic constraint, essential for the induction of stable secondary structures, determines the biomimetic potential of such molecules, which act as antimicrobials, cytotoxic agents, siderophores, glycosidases inhibitors and so on. The bioactivity can be either attributed to the macrocyclic core (especially chelation) or to the side‐chains (when endowed with specific groups or pharmacophores). The structure‐bioactivity correlations emerging for this class of peptidomimetics, based on the study of conformational order and morphology of the backbone architecture, unravel interesting avenues for the rational design of more effective cyclooligomeric biomimics.

The quest for a conifold conformal order

The holographic duality between cascading gauge theory and type IIB supergravity on warped deformed conifold with fluxes reveals exotic thermal phases with nonzero expectation values of certain operators, persistent to high temperatures. These phases, in the limit of vanishing the strong coupling scale of the cascading gauge theory, would realize thermal ordered conformal phases in ℝ3,1 relativistic QFT. We find that the dual Klebanov-Strassler/Klebanov-Tseytlin black branes in this limit are outside the regime of the supergravity approximation, rendering the construction of such conformal ordered states unreliable. While we have been able to construct conformal order in phenomenologically deformed effective theory of type IIB supergravity reduced on warped deformed conifold with fluxes, the removal of the deformation parameter causes the destruction of the thermal conformal ordered phases. Once again, we find that the holographic models with the conformal ordered phases are in the String Theory swampland.

On characterisations of the input to state stability properties for conformable fractional order bilinear systems

This paper proposes for the first time the theoretical requirements that a fractional-order bilinear system with conformable derivative has to fulfil in order to satisfy different input-to-state stability (ISS) properties. Variants of ISS, namely ISS itself, integral ISS, exponential integral ISS, small-gain ISS, and strong integral ISS for the general class of conformable fractional-order bilinear systems are investigated providing a set of necessary and sufficient conditions for their existence and then compared. Finally, the correctness of the obtained theoretical results is verified by numerical example.

A Nonlinear Triaxial Damage Creep Model for Granite Based on Atangana–Baleanu Fractional Derivative

Finding a fractional derivative that can more accurately describe the characteristics of a dynamic process is one of the objectives for fractional derivative modeling. In this paper, Atangana–Baleanu (AB) fractional order dashpots with constant and variable coefficients are constructed by using AB fractional derivatives with nonlocal and nonsingular kernel characteristics. Compared with Riemann–Liouville (RL) and conformable (KA) fractional order dashpot, AB fractional order dashpot can describe the viscoelastic properties of materials in full time. A new damage AB fractional derivative (DABFD) creep model is proposed by improving the Nishihara model with the help of the variable coefficient AB fractional dashpot. The parameters for the DABFD creep model are determined by fitting creep experimental data of Beishan granite. Compared with the Nishihara, damage RL fractional derivative (DRLFD) and damage KA fractional derivative (DKAFD) creep models, DABFD creep model has a better fitting and prediction accuracy. The parameter sensitivity for the DABFD creep model shows that different creep curves can be demonstrated with different DABFD creep model parameters. The model can better represent the viscoelastic properties and three stages of the creep process for rock.

A Conformable Fractional Discrete Grey Model CFDGM (1,1) and its Application

An accurate forecast of the area of drought disaster is vitally important for the government to take appropriate measures to prevent disaster. In the current study, a new conformable fractional discrete grey model is applied to study the trend of the area affected by drought disasters. Firstly, the new model, abbreviated as CFDGM(1,1), is proposed with the definitions of the conformable fractional operator and the classical GM(1,1) model. Then the recursive expression of the time response function is obtained by the grey basic form, and the linear system parameters are confirmed by the linear least squares method. Further, the Salp Swarm Algorithm is chosen to determine the optimal conformable fractional order. Finally, the area of drought disaster is studied by the new model and others, where the results show the new model has a good performance among these models.

Conformable Fractional Order Controller Design and Implementation for Per-Phase Voltage Regulation of Three-Phase SEIG Under Unbalanced Load

Self-excited induction generators (SEIGs) usage is an effective way to generate electrical power in off-grid locations. This study aims to performance improvement for voltage regulation of the SEIG in wind turbine systems. To achieve this, a fixed-capacitor with thyristor controlled-reactor based per-phase voltage controller is designed with a conformable fractional order proportional integral (CFOPI) method. The SEIG system is modeled based on small signal analysis by using the input-output data, experimentally. To do this, system identification toolbox of Matlab is used. The proposed controller is established on conformable fractional integral approach proposed by Khalil et al. in 2014. Proposed CFOPI controller parameters Kp , Ki and γ are optimized using particle swarm optimization (PSO) according to minimization of integral time absolute error (ITAE). To validate the success of proposed scheme, CFOPI, traditional fractional order PI (TFOPI) and integer order PI (IOPI) controllers are tested under same experimental setup and results are compared. Three experiments, after voltage build-up process, under balanced and unbalanced load are done for each controller. Experimental results demonstrate that proposed voltage regulator improves the performance of SEIG systems. Moreover, robust voltage regulation is ensured thanks to independent control loops created for each phase.

Stretching effect on intrachain conformational ordering of polymers: A steered molecular dynamics simulation

The stretching effect on the intrachain conformational ordering of PE, i PP and i PB-1 single chains was investigated using all-atom steered molecular dynamics simulations. We observed frequent helical reversals and competition between different chirality in i PP and i PB-1 chains during cooling. Simulation results show that imposing proper stretch can greatly promote the formation of helical structures of i PP and i PB-1 chains. Stretch can also cause the helicity transition between 3/1 and 11/3 helix for i PB-1. Generally, stretching with proper force elevates the helix-forming temperature while too large force can cause the instability and even destruction of helices. The end-to-end distance of chains with different stretching force is suggested the control factor of helix formation. Deviation from the optimum helical size results in weakened promotion of helix formation in some extent, and finally leads to the destruction of helical structures. Our results are helpful for understanding the crystallization of helical polymers and the transition between crystalline modifications. • Stretching properly promotes helix formation while overstretch can destroy it. • The helical reversal pathway between different chirality is pointed out. • The R ee of chains with stretching influences the helix formation greatly. • There is a significant impact of stretching on the stable helicity for iPB-1.

Substrate roughness influence on the order of nanografted Self-Assembled Monolayers

Adjacent patches of alkanethiol molecules whose chain lengths range from 11 to 15 carbon atoms are fabricated by nanografting within a Self-Assembled Monolayer matrix. Atomic Force Microscopy and Electrostatic Force Microscopy are employed to investigate their structural and electronic properties, highlighting the key role of the substrate roughness. In particular, the topographic phase signal allows to establish an odd–even dependence of the local stiffness versus the alkyl chain length, while the electrostatic force signal provides evidence that the conformational order versus the alkyl chain length follows an asymmetric parabolic trend induced by the substrate roughness.

General Principles Underpinning Amyloid Structure.

Amyloid fibrils are a pathologically and functionally relevant state of protein folding, which is generally accessible to polypeptide chains and differs fundamentally from the globular state in terms of molecular symmetry, long-range conformational order, and supramolecular scale. Although amyloid structures are challenging to study, recent developments in techniques such as cryo-EM, solid-state NMR, and AFM have led to an explosion of information about the molecular and supramolecular organization of these assemblies. With these rapid advances, it is now possible to assess the prevalence and significance of proposed general structural features in the context of a diverse body of high-resolution models, and develop a unified view of the principles that control amyloid formation and give rise to their unique properties. Here, we show that, despite system-specific differences, there is a remarkable degree of commonality in both the structural motifs that amyloids adopt and the underlying principles responsible for them. We argue that the inherent geometric differences between amyloids and globular proteins shift the balance of stabilizing forces, predisposing amyloids to distinct molecular interaction motifs with a particular tendency for massive, lattice-like networks of mutually supporting interactions. This general property unites previously characterized structural features such as steric and polar zippers, and contributes to the long-range molecular order that gives amyloids many of their unique properties. The shared features of amyloid structures support the existence of shared structure-activity principles that explain their self-assembly, function, and pathogenesis, and instill hope in efforts to develop broad-spectrum modifiers of amyloid function and pathology.

Exploratory in vivo biophysical studies of stratum corneum lipid organization in human face and arm skin

The purpose of this in vivo exploratory study was to investigate human stratum corneum (SC) lipid conformational order and chain packing in healthy face (cheek) skin as a function of stratum corneum depth using a combination of tape-stripping and horizontal attenuated total reflection Fourier transform infrared (HATR-FTIR) spectroscopy. Equivalent data were also collected from volar forearm skin as we, and others, have previously characterized forearm SC lipid order as a function of depth, therefore these data served as a comparison site and an experimental internal standard for the previously unmeasured in vivo face skin data. An SC depth profile was achieved by using tape strips to sequentially remove “layers” of SC. Trans epidermal water loss (TEWL) measurements were recorded following each sequential tape strip. In vivo HATR-FTIR spectra were collected after each tape strip, providing a depth profile of spectral data through the SC of both faces and arms. Spectral data were analyzed at five discrete SC depths corresponding to baseline and SC depths at which the increase in TEWL was 25, 50, 75, and 100 percent (%) from the baseline measurement. Analysis of the SC in vivo HATR-FTIR spectroscopic data utilized mean spectra generated by averaging the spectra from all panelists (n = 10) at the five specific SC depths corresponding to when TEWL had increased by 25, 50, 75 and 100 % from baseline for each subject, respectively. While this is an exploratory study, and the data could be collated and processed in many ways, the average spectral data reveal clear trends in the face and arm SC. Increasing SC lipid order with depth is observed for face skin, as with arm skin, albeit with significant differences at all relative depths in the absolute lipid order between faces and arms. In vivo SC lipids are significantly more ordered at all depths in arms versus cheeks. The less ordered SC lipids of face skin can be in part attributed to the presence of a high amount of fluid sebaceous lipid species observed deep into the face SC. Interestingly, no evidence of orthorhombic packing is observed at any depth in face SC. This is consistent with the high degree of disorder indicated from the chain fluidity measurements. These in vivo HATR-FTIR depth studies of face skin highlight how different SC barrier organization is in the face compared to the more widely studied body sites such as arms and legs. Further studies of the SC lipid barrier in faces are needed to understand the significant differences in lipid organization and its implication for the penetration of drug and cosmetic actives through face skin.

Minimal Increments of Hydrophobic Collapse within the N-Terminus of the Neuropeptide Galanin.

The neuropeptide galanin has a 35-year history as an intriguing target in drug design owing to its implication as a potential anticonvulsant and neuronal trophic factor among many other therapeutically interesting functions including analgesia and mood alteration. In this study, we report the structural characterization of three synthetic fragments of the galanin N-terminus in buffered aqueous solution: hGal(2-12)KK, hGal(1-12)KK, and hGal(1-17)KK. High-field two-dimensional 1H-1H nuclear magnetic resonance (NMR) data were acquired for these fragments and used to derive distance restraints. We further utilized modified hydrogen bonding and dihedral restraints to reflect chemical shift patterns in the data, which revealed the signature of a weakly folded helix. Together, these sets of restraints were used to generate NMR structures of all three fragments, which depict a core of hydrophobic residues that cluster together regardless of the presence of a helical structure, and correspond to residues in the N-terminus of galanin that have been previously shown to be critical for binding its receptors. The helical structure only appears following the inclusion of Gly(1) in the sequence, and at longer sequence lengths, unlike many other peptides, the helix does not propagate. Rather, a few turns of poorly ordered helix appear to be a secondary consequence of clusters of hydrophobic sidechains that are conserved across all of the peptides in this study; the helices themselves appear ordered as a consequence of this clustering, and these clusters compare directly to those observed recently to make contacts between galanin and two of its receptor subtypes. Collapsed hydrophobic residues therefore organize and compose the functional core of human galanin and raise interesting questions about the nature of the conformational order in ligands that bind cell surface receptors.

Flavour compounds affect protein structure: The effect of methyl anthranilate on bovine serum albumin conformation

This study aims to understand possible effects of flavour compounds on the structure and conformation of endogenous proteins. Using methyl anthranilate (a grape flavour compound added to drinks, confectionery, and vape-liquids) and bovine serum albumin (BSA, a model serum protein) we designed experimental investigations using analytical ultracentrifugation, size exclusion chromatography small angle X-ray scattering, and fluorescence spectroscopy to reveal that methyl anthranilate spontaneously binds to BSA (ΔG°, ca. −21 KJ mol−1) which induces a conformational compactness (ca. 10 %) in the monomer structure. Complementary molecular modelling and dynamics simulations suggested the binding occurs at Sudlow II of BSA via establishment of hydrogen bonds with arginine409, lysine413 and serine488 leading to an increased conformational order in domains IA, IIB and IIIB. This work aims to set the foundation for future research on flavour-protein interactions and offer new sets of opportunities for understanding the effects of small compounds on protein structure.

Modelo matemático para estimar el coeficiente volumétrico de transferencia de oxígeno en biorreactores usando cálculo conformal

This work proposes a novel mathematical model based on time conformable derivative convective mass transfer equation to calculate the volumetric oxygen transfer coefficient (kLa) in a bioreactor. To validate the novel model, a full mixed-level experimental design was proposed with two factors: agitation speed and dispersed phase. The model employs the conformable derivate order operator (α) and the electrode constant (kp), which changes with electrode use and the operating conditions of the bioreactor. The results show that when the viscosity increases and the agitation decreases, the value α increases, and vice versa. Therefore, α is a parameter that has a physical meaning in the process. The correlation coefficient of the proposed model with the experimental data (R2 > 0.985) is higher than the one obtained with conventional models. The Akaike information criterion determined that the proposed conformal model describes the experimental data by 59%, while the conventional models describe the experimental data by 25% and 15%. There are no reports of similar mathematical models that determine mass transfer coefficients in bioprocesses.

Conformational state diagram of DOPC/DPPCd62/cholesterol mixtures.

Raman spectra of aqueous suspensions of vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), deuterated 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (DPPCd62), and cholesterol (Chol) were studied at room temperature to determine the conformational states of the phospholipid hydrocarbon chains. Deuteration of DPPCd62 allowed us to characterize the conformational states of DOPC and DPPCd62 independently. The parameters of Raman peaks, which are sensitive to the conformational order, were studied in a wide range of compositions. It was found that the DOPC molecules are conformationally disordered for all compositions. The conformational state of the DPPCd62 molecules changes with composition. Their conformational state is influenced by cholesterol-induced partial disordering and DOPC solvation, transforming the DPPC molecules into the disordered state. The conformational state diagram from the Raman experiment was compared with outcomes from the differential scanning calorimetry (DSC) experiment. The Raman spectra also revealed that the DPPC molecules coexist in the disordered and all-trans ordered states for the DOPC/DPPCd62/Chol mixtures except for the pure liquid-disordered phase.

Mathematical analysis and numerical simulation of the Ebola epidemic disease in the sense of conformable derivative

The aim of this paper is to construct and analyze a mathematical model for the response of T-cytotoxic lymphocytes to the Ebola virus using the Herz-tuckwill model with nonlinear Conformable order differential equations which derive from real biological data, then study the global stability of the equilibria using an appropriate Lyapunov function and the LaSalle invariance principle. Furthermore, we demonstrate the impact of the non-integer order of the model compared with the integral order. Finally consider a numerical simulation that justifies the biological hypotheses and the theory results. The numerical results provided that, the non-integer order has a great impact on the treatments of Ebola virus in this model.

Separations by Shape: Molecular Shape Recognition in Liquid Chromatography.

Molecular shape can provide a basis for chromatographic separations that is distinct from other interaction mechanisms often considered in liquid chromatography. Molecular shape recognition, or shape selectivity, is most evident for the separation of isomeric compounds that have constrained molecular structures, such as polycyclic aromatic hydrocarbons. A central feature of shape-selective columns is conformational order within the stationary phase; this aspect of stationary phase morphology is revealed through spectroscopic studies and molecular dynamics simulations, and is correlated with chromatographic performance.

Surface functionalization strategy to enhance the antibacterial effect of nisin Z peptide

One of the main challenges when building antibacterial surfaces with antimicrobial peptides (AMPs) is to preserve their antimicrobial activity after stable immobilization of the peptides. Among all parameters, order/conformation of self-assembled monolayers, used as spacer, is one the most important. Herein we report the covalent immobilization of the nisin Z peptide on a gold surface functionalized with a self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) alone or mixed with 6-mercaptohexanol, used as a spacer. The MUA acid is activated by treatment with carbodiimide/N-hydroxysuccinimidine and then reacts with nisin Z to form amide bonds via the N terminal part of the peptide. We have characterized each step of the surface modification using X-ray photoelectron spectroscopy, FTIR-ATR spectroscopy and contact angle measurements. The combined results show the success of each functionalization step. Additionally, SFG brings information on the orientation and conformational ordering of the self-assembled monolayers. Indeed, a better order of MUA25 layers compared to MUA was observed due to the spacing of carboxylic acid groups. The antibacterial activity of the immobilized AMPs against Staphylococcus aureus is evaluated using confocal microscopy and bacterial counting: it increases with a better order of the SAMs rather than a greater peptide concentration. This study provides fundamental insights on how to engineer AMPs and substrate to produce efficient biocidal surfaces.

Conformable fractional order controller design and optimization for sensorless control of induction motor

PurposeIn recent years, use of sensorless control methods for electrical motor-based variable speed drive systems has been increasing rapidly to compensate the increasing costs in industrial systems. Also, use of induction motors is popular for a long time to decrease the cost of these industrial systems. This study aims to design an effective controller to improve the sensorless speed control performance of induction motor. To achieve this, a conformable fractional order proportional integral (CFOPI) controller is designed.Design/methodology/approachThe system is modeled based on small signal analysis by using the input–output data, experimentally. To do this, system identification toolbox of Matlab is used. The proposed controller is established on conformable fractional integral approach proposed by Khalil et al. (2014). CFOPI controller coefficients are optimized using particle swarm optimization method on the created small signal-based simulation model of the system to minimize the integral time absolute error. To prove the success of the proposed method, a traditional fractional order proportional integral (TFOPI) controller is tested under the same experimental system with the CFOPI controller.FindingsTFOPI and CFOPI controllers are tested with the optimum parameters. Reference and actual speed trends are obtained for both methods. In induction motor start-up test, settling-times are measured as 8.73 and 8.44 s and steady-state oscillations are 2.66% and 0% (almost) for TFOPI and CFOPI controllers, respectively. In variable referenced speed tracking test, CFOPI performs well at all speed levels, while TFOPI fails to reach the reference speed at most speed levels.Practical implicationsProposed CFOPI control method can be easily implemented in industrial systems, thanks to its simple algorithm. digital signal peripheral interface controller (dsPIC) based driver circuit with designed CFOPI controller used in this study can be applied directly to industrial systems such as elevators, conveyors, cranes and drills. Moreover, it can improve the performance of induction motor-based variable speed drive systems.Originality/valueThe proposed method provides robust performance for induction motor used in control systems. Additionally, it does this by using less complex algorithm written on the processors according to the traditional fractional order controllers.

Time-resolved DEER EPR and solid-state NMR afford kinetic and structural elucidation of substrate binding to Ca2+-ligated calmodulin

Recent advances in rapid mixing and freeze quenching have opened the path for time-resolved electron paramagnetic resonance (EPR)-based double electron-electron resonance (DEER) and solid-state NMR of protein-substrate interactions. DEER, in conjunction with phase memory time filtering to quantitatively extract species populations, permits monitoring time-dependent probability distance distributions between pairs of spin labels, while solid-state NMR provides quantitative residue-specific information on the appearance of structural order and the development of intermolecular contacts between substrate and protein. Here, we demonstrate the power of these combined approaches to unravel the kinetic and structural pathways in the binding of the intrinsically disordered peptide substrate (M13) derived from myosin light-chain kinase to the universal eukaryotic calcium regulator, calmodulin. Global kinetic analysis of the data reveals coupled folding and binding of the peptide associated with large spatial rearrangements of the two domains of calmodulin. The initial binding events involve a bifurcating pathway in which the M13 peptide associates via either its N- or C-terminal regions with the C- or N-terminal domains, respectively, of calmodulin/4Ca2+ to yield two extended "encounter" complexes, states A and A*, without conformational ordering of M13. State A is immediately converted to the final compact complex, state C, on a timescale τ ≤ 600 μs. State A*, however, only reaches the final complex via a collapsed intermediate B (τ ∼ 1.5 to 2.5 ms), in which the peptide is only partially ordered and not all intermolecular contacts are formed. State B then undergoes a relatively slow (τ ∼ 7 to 18 ms) conformational rearrangement to state C.

Consensus of linear conformable fractional order multi‐agent systems with impulsive control protocols

AbstractIn this article, we study the impulsive consensus problem of linear multi‐agent systems composed of α‐order conformable differential equations (α ∈ (0, 1]). Two cases of fixed and switching interaction networks are considered, respectively. Impulsive protocol of each agent is introduced based on the local information of the interaction networks. Firstly, we derive the analytic solution of the general linear conformable systems with impulses. Secondly, two sufficient criterions are presented to guarantee the convergence of the consistent state for all the agents by using matrix theory, graph theory, and impulsive control theory. Finally, three numerical simulations are provided to demonstrate the obtained theoretical results and to compare the convergence rates of the systems with distinct orders.