scholarly journals Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 449
Author(s):  
Weria Pezeshkian ◽  
Julian C. Shillcock ◽  
John H. Ipsen
Keyword(s):  
Cell Membrane ◽  
Rational Design ◽  
Protein Complexes ◽  
Coarse Grained ◽  
Bacterial Toxin ◽  
Special Focus ◽  
Specific Substrate ◽  
Mesoscopic Models ◽  
Recent Developments ◽  
Entry Mechanism

Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein complexes is essential not only for understanding their biological functions but also for the rational design of targeted drug delivery vehicles that must navigate across the cell membrane to deliver their therapeutic payload. Despite the immense advances in experimental techniques, the investigations of the toxin entry mechanism have remained challenging. Computer simulations are robust complementary tools that allow for the exploration of biological processes in exceptional detail. In this review, we first highlight the strength of computational methods, with a special focus on all-atom molecular dynamics, coarse-grained, and mesoscopic models, for exploring different stages of the toxin protein entry mechanism. We then summarize recent developments that are significantly advancing our understanding, notably of the glycolipid–lectin (GL-Lect) endocytosis of bacterial Shiga and cholera toxins. The methods discussed here are also applicable to the design of membrane-penetrating nanoparticles and the study of the phenomenon of protein phase separation at the surface of the membrane. Finally, we discuss other likely routes for future development.

Mass Spectrometry for Proteomics and Recent Developments in ESI, MALDI and other Ionization Methodologies

2019 ◽  
Vol 16 (4) ◽  
pp. 267-276
Author(s):  
Qurat ul Ain Farooq ◽  
Noor ul Haq ◽  
Abdul Aziz ◽  
Sara Aimen ◽  
Muhammad Inam ul Haq
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
New Technologies ◽  
Protein Complexes ◽  
Imaging Techniques ◽  
Desorption Electrospray Ionization ◽  
High Throughput Analysis ◽  
Enhanced Sensitivity ◽  
Recent Developments ◽  
The Way

Background: Mass spectrometry is a tool used in analytical chemistry to identify components in a chemical compound and it is of tremendous importance in the field of biology for high throughput analysis of biomolecules, among which protein is of great interest. Objective: Advancement in proteomics based on mass spectrometry has led the way to quantify multiple protein complexes, and proteins interactions with DNA/RNA or other chemical compounds which is a breakthrough in the field of bioinformatics. Methods: Many new technologies have been introduced in electrospray ionization (ESI) and Matrixassisted Laser Desorption/Ionization (MALDI) techniques which have enhanced sensitivity, resolution and many other key features for the characterization of proteins. Results: The advent of ambient mass spectrometry and its different versions like Desorption Electrospray Ionization (DESI), DART and ELDI has brought a huge revolution in proteomics research. Different imaging techniques are also introduced in MS to map proteins and other significant biomolecules. These drastic developments have paved the way to analyze large proteins of >200kDa easily. Conclusion: Here, we discuss the recent advancement in mass spectrometry, which is of great importance and it could lead us to further deep analysis of the molecules from different perspectives and further advancement in these techniques will enable us to find better ways for prediction of molecules and their behavioral properties.

KINETIC SURFACE ROUGHENING AND MOLECULAR BEAM EPITAXY

Fractals ◽  
1993 ◽  
Vol 01 (04) ◽  
pp. 784-794 ◽  
Author(s):  
S. DAS SARMA
Keyword(s):  
Molecular Beam Epitaxy ◽  
Molecular Beam ◽  
Growth Conditions ◽  
Coarse Grained ◽  
Solid State Physics ◽  
Growth Phenomenon ◽  
Recent Developments ◽  
Growth Equations ◽  
Universality Classes ◽  
Actual Growth

We review recent developments in our understanding of Molecular Beam Epitaxy as a kinetically rough growth phenomenon. It is argued that while the most general growth conditions lead to generic growth universality, actual growth conditions allow a complex interplay of several different dynamic universality classes producing rich crossover behavior determined by growth temperature, incident flux rate, and local solid state physics and chemistry of the growing material. Possible coarse-grained continuum growth equations which may be applicable to Molecular Beam Epitaxy are discussed.

scholarly journals Gelation Impairs Phase Separation and Small Molecule Migration in Polymer Mixtures

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1576
Author(s):  
Biswaroop Mukherjee ◽  
Buddhapriya Chakrabarti
Keyword(s):  
Phase Separation ◽  
Rational Design ◽  
Surface Segregation ◽  
Multiscale Methods ◽  
Coarse Grained ◽  
Polymer Gel ◽  
Polymer Mixtures ◽  
Separation Processes ◽  
Surface Migration ◽  
Wide Range

Surface segregation of the low molecular weight component of a polymeric mixture is a ubiquitous phenomenon that leads to degradation of industrial formulations. We report a simultaneous phase separation and surface migration phenomena in oligomer–polymer ( O P ) and oligomer–gel ( O G ) systems following a temperature quench that induces demixing of components. We compute equilibrium and time varying migrant (oligomer) density profiles and wetting layer thickness in these systems using coarse grained molecular dynamics (CGMD) and mesoscale hydrodynamics (MH) simulations. Such multiscale methods quantitatively describe the phenomena over a wide range of length and time scales. We show that surface migration in gel–oligomer systems is significantly reduced on account of network elasticity. Furthermore, the phase separation processes are significantly slowed in gels leading to the modification of the well known Lifshitz–Slyozov–Wagner (LSW) law ℓ ( τ ) ∼ τ 1 / 3 . Our work allows for rational design of polymer/gel–oligomer mixtures with predictable surface segregation characteristics that can be compared against experiments.

scholarly journals Advances in Single-Cell Printing

Micromachines ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 80
Author(s):  
Xiaohu Zhou ◽  
Han Wu ◽  
Haotian Wen ◽  
Bo Zheng
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Three Dimensional ◽  
Cell Isolation ◽  
Special Focus ◽  
Cell Analysis ◽  
Cell Array ◽  
Cell Printing ◽  
Recent Developments ◽  
Single Cell Isolation

Single-cell analysis is becoming an indispensable tool in modern biological and medical research. Single-cell isolation is the key step for single-cell analysis. Single-cell printing shows several distinct advantages among the single-cell isolation techniques, such as precise deposition, high encapsulation efficiency, and easy recovery. Therefore, recent developments in single-cell printing have attracted extensive attention. We review herein the recently developed bioprinting strategies with single-cell resolution, with a special focus on inkjet-like single-cell printing. First, we discuss the common cell printing strategies and introduce several typical and advanced printing strategies. Then, we introduce several typical applications based on single-cell printing, from single-cell array screening and mass spectrometry-based single-cell analysis to three-dimensional tissue formation. In the last part, we discuss the pros and cons of the single-cell strategies and provide a brief outlook for single-cell printing.

scholarly journals Endogenous and exogenous electric fields as modifiers of brain activity: rational design of noninvasive brain stimulation with transcranial alternating current stimulation

2014 ◽  
Vol 16 (1) ◽  
pp. 93-102 ◽  
Keyword(s):  
Electric Fields ◽  
Brain Stimulation ◽  
Rational Design ◽  
Brain Activity ◽  
Field Potential ◽  
Alternating Current ◽  
Noninvasive Brain Stimulation ◽  
Starting Point ◽  
Recent Developments ◽  
Transcranial Alternating Current Stimulation

Synchronized neuronal activity in the cortex generates weak electric fields that are routinely measured in humans and animal models by electroencephalography and local field potential recordings. Traditionally, these endogenous electric fields have been considered to be an epiphenomenon of brain activity. Recent work has demonstrated that active cortical networks are surprisingly susceptible to weak perturbations of the membrane voltage of a large number of neurons by electric fields. Simultaneously, noninvasive brain stimulation with weak, exogenous electric fields (transcranial current stimulation, TCS) has undergone a renaissance due to the broad scope of its possible applications in modulating brain activity for cognitive enhancement and treatment of brain disorders. This review aims to interface the recent developments in the study of both endogenous and exogenous electric fields, with a particular focus on rhythmic stimulation for the modulation of cortical oscillations. The main goal is to provide a starting point for the use of rational design for the development of novel mechanism-based TCS therapeutics based on transcranial alternating current stimulation, for the treatment of psychiatric illnesses.

Recent Developments of Micropattern Detectors

2014 ◽  
pp. 156-194
Keyword(s):  
Large Hadron Collider ◽  
Visible Light ◽  
Parallel Plate ◽  
Hadron Collider ◽  
Special Focus ◽  
Large Area ◽  
Special Place ◽  
Recent Developments ◽  
New Generation ◽  
Detector Technology

In this chapter, the exciting developments in micropattern detectors in recent years are described. This includes GEM and MICROMEGAS detectors combined with micropixel readout, some peculiar designs of GEM and GEM-like detectors sensitive to UV and visible light, large area (>1m2) GEM and MICROMEGAS prototypes developed for the upgrades of the experiments at the large hadron collider, etc. A special focus is put on a new generation of spark-proof micropattern detectors, using resistive electrodes instead of traditional metallic ones. These detectors operate as ordinary micropattern detectors. However, in the case of occasional sparks, their current is limited by the resistivity of the electrodes so that the energy of the discharge is reduced by several orders of magnitude. Various designs of such detectors have been developed and successfully tested, including resistive GEM, resistive MICROMEGAS, resistive MSGC, etc. Among this family of detectors, a special place belongs to resistive parallel-plate micropattern detectors allowing one to achieve at the same time excellent spatial (38 µm) and time (77 ps) resolutions. Finally, the potential of multilayer detector technology for further optimization of the detector operation is discussed.

UNRES-Dock—protein–protein and peptide–protein docking by coarse-grained replica-exchange MD simulations

2020 ◽  
Author(s):  
Paweł Krupa ◽  
Agnieszka S Karczyńska ◽  
Magdalena A Mozolewska ◽  
Adam Liwo ◽  
Cezary Czaplewski
Keyword(s):  
Protein Complexes ◽  
Md Simulations ◽  
Protein Docking ◽  
Conformational Space ◽  
Coarse Grained ◽  
Supplementary Information ◽  
Replica Exchange ◽  
Variable Degree ◽  
Single Chain ◽  
Simulation Speed

Abstract Motivation The majority of the proteins in living organisms occur as homo- or hetero-multimeric structures. Although there are many tools to predict the structures of single-chain proteins or protein complexes with small ligands, peptide–protein and protein–protein docking is more challenging. In this work, we utilized multiplexed replica-exchange molecular dynamics (MREMD) simulations with the physics-based heavily coarse-grained UNRES model, which provides more than a 1000-fold simulation speed-up compared with all-atom approaches to predict structures of protein complexes. Results We present a new protein–protein and peptide–protein docking functionality of the UNRES package, which includes a variable degree of conformational flexibility. UNRES-Dock protocol was tested on a set of 55 complexes with size from 43 to 587 amino-acid residues, showing that structures of the complexes can be predicted with good quality, if the sampling of the conformational space is sufficient, especially for flexible peptide–protein systems. The developed automatized protocol has been implemented in the standalone UNRES package and in the UNRES server. Availability and implementation UNRES server: http://unres-server.chem.ug.edu.pl; UNRES package and data used in testing of UNRES-Dock: http://unres.pl. Supplementary information Supplementary data are available at Bioinformatics online.

Bribery: cost of doing business in Africa

2017 ◽  
Vol 24 (1) ◽  
pp. 56-64
Author(s):  
Adefolake Adeyeye
Keyword(s):  
Secondary Data ◽  
Primary Data ◽  
Special Focus ◽  
Journal Articles ◽  
Content Type ◽  
Doing Business ◽  
Recent Developments ◽  
Research Findings ◽  
Media Reports ◽  
Available Information

Purpose The purpose of this paper is to examine the implications of foreign bribery and perceptions that bribery is just a cost of doing business in Africa in light of recent reports and developments in the global attempt to curb bribery and corruption. Design/methodology/approach The research relied on primary data from anti-corruption legislation, surveys and monitoring reports and secondary data from publicly available information, journal articles and media reports to analyse recent developments in the fight against corruption with a special focus on Africa. Findings The research findings and analysis suggest that foreign bribery, which is illegal but largely carried out with impunity and perceived as a just a cost of doing business in Africa, has heavy costs on developing nations and on corporations and individuals that are prosecuted. Although much has been done to curb corruption, it seems active enforcement takes place in only a limited number of countries. There is still the need for enhanced enforcement by nations, increased societal awareness of effective measures against corruption and improved corporate compliance and responsibility. Originality/value The paper contributes practical insights into improvements and lapses in the fight against foreign bribery and corruption. Using recent and relevant analysis, the paper revisits the resilience of bribery and corruption in spite of increased anti-corruption actions and the need for multiple and varied measures. The information provided will be useful for governments, corporations and civil society in the fight against corruption, which requires constant multilateral action and examination.

Metalloligand Strategies for Assembling Heteronuclear Nanocages – Recent Developments

2019 ◽  
Vol 72 (10) ◽  
pp. 731 ◽  
Author(s):  
Feng Li ◽  
Leonard F. Lindoy
Keyword(s):  
Structural Properties ◽  
Metal Ion ◽  
Rational Design ◽  
Building Blocks ◽  
Structural Elements ◽  
Present Discussion ◽  
The Past ◽  
Recent Developments ◽  
Metal Organic ◽  
Multifunctional Ligand

The use of metalloligands as building blocks for the assembly of metallo-organic cages has received increasing attention over the past two decades or so. In part, the popularity of this approach reflects its stepwise nature that lends itself to the predesigned construction of metallocages and especially heteronuclear metallocages. The focus of the present discussion is on the use of metalloligands for the construction of discrete polyhedral cages, very often incorporating heterometal ions as structural elements. The metalloligand approach uses metal-bound multifunctional ligand building blocks that display predesigned structural properties for coordination to a second metal ion such that the rational design and construction of both homo- and heteronuclear metal–organic cages are facilitated. The present review covers published literature in the area from early 2015 to early 2019.

Cryo-Electron Microscopy: Moving Beyond X-Ray Crystal Structures for Drug Receptors and Drug Development

2020 ◽  
Vol 60 (1) ◽  
pp. 51-71 ◽  
Author(s):  
Javier García-Nafría ◽  
Christopher G. Tate
Keyword(s):  
Membrane Proteins ◽  
G Protein ◽  
Rational Design ◽  
Protein Complexes ◽  
Host Cells ◽  
X Ray ◽  
X Ray Crystallography ◽  
Receptor Modulation ◽  
Lipid Environment ◽  
Drug Receptors

Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent progress in the field of drug receptors, focusing on cryo-EM of two protein families with established therapeutic value, the γ-aminobutyric acid A receptors (GABAARs) and G protein–coupled receptors (GPCRs). GABAARs are pentameric ion channels, and cryo-EM structures of physiological heteromeric receptors in a lipid environment have uncovered the molecular basis of receptor modulation by drugs such as diazepam. The structures of ten GPCR–G protein complexes from three different classes of GPCRs have now been determined by cryo-EM. These structures give detailed insights into molecular interactions with drugs, GPCR–G protein selectivity, how accessory membrane proteins alter receptor–ligand pharmacology, and the mechanism by which HIV uses GPCRs to enter host cells.

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