scholarly journals Integrative Modeling of Membrane-associated Protein Assemblies

2020 ◽  
Author(s):  
Jorge Roel-Touris ◽  
Brian Jiménez-García ◽  
Alexandre M.J.J. Bonvin
Keyword(s):  
Membrane Proteins ◽  
Coarse Grained ◽  
Protein Assemblies ◽  
Topological Information ◽  
Modeling Process ◽  
Cryo Electron Microscopy ◽  
Docking Protocol ◽  
Rigid Body Docking ◽  
Shed Light

AbstractHistorically, membrane protein systems have been considered as one of the most challenging systems to study with experimental structural biology techniques. Over the past years, increased number of experimental structures of membrane proteins have become available thanks in particular to advances in solid-state NMR spectroscopy and cryo-electron microscopy. This has opened the route to modeling the complexes that those membrane proteins form by methods such as docking. Most approaches developed to date are, however, not capable of incorporating the topological information provided by the membrane into the modeling process. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies, specifically complexes consisting of a membrane-embedded protein and a soluble partner. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We make use of an equilibrated coarse-grained lipid bilayer to represent the information encoded in the membrane in the form of artificial beads, which allows to target the docking towards the binding-competent regions. We demonstrate the performance of this membrane-driven protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we evaluate how different membrane definitions impact the performance of the docking protocol and provide a comparison, in terms of success rate, to another state-of-the-art docking software, ZDOCK. Finally, we discuss the quality of the generated models and propose possible future developments. Our membrane docking protocol should allow to shed light on the still rather dark fraction of the interactome consisting of membrane proteins.

scholarly journals Integrative modeling of membrane-associated protein assemblies

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jorge Roel-Touris ◽  
Brian Jiménez-García ◽  
Alexandre M. J. J. Bonvin
Keyword(s):  
Artificial Intelligence ◽  
Membrane Proteins ◽  
Rigid Body ◽  
Structural Biology ◽  
State Of The Art ◽  
Protein Assemblies ◽  
Integrative Modeling ◽  
Rigid Body Docking ◽  
Shed Light ◽  
Computational Protocol

AbstractMembrane proteins are among the most challenging systems to study with experimental structural biology techniques. The increased number of deposited structures of membrane proteins has opened the route to modeling their complexes by methods such as docking. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies. The information encoded by the membrane is represented by artificial beads, which allow targeting of the docking toward the binding-competent regions. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We demonstrate the performance of this protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we provide a comparison to another state-of-the-art docking software, ZDOCK. This protocol should shed light on the still dark fraction of the interactome consisting of membrane proteins.

The Baluch, Sunnism and the State in Iran

2017 ◽  
Author(s):  
Stéphane A. Dudoignon
Keyword(s):  
South Asia ◽  
South Asian ◽  
Social Life ◽  
The State ◽  
First Century ◽  
Local Democracy ◽  
Oasis Area ◽  
Shed Light

Since 2002, Sunni jihadi groups have been active in Iranian Baluchistan without managing to plunge the region into chaos. This book suggests that a reason for this, besides Tehran’s military responses, has been the quality of Khomeini and Khamenei’s relationship with a network of South-Asia-educated Sunni ulama (mawlawis) originating from the Sarbaz oasis area, in the south of Baluchistan. Educated in the religiously reformist, socially conservative South Asian Deoband School, which puts the madrasa at the centre of social life, the Sarbazi ulama had taken advantage, in Iranian territory, of the eclipse of Baluch tribal might under the Pahlavi monarchy (1925-79). They emerged then as a bulwark against Soviet influence and progressive ideologies, before rallying to Khomeini in 1979. Since the turn of the twenty-first century, they have been playing the role of a rampart against Salafi propaganda and Saudi intrigues. The book shows that, through their alliance with an Iranian Kurdish-born Muslim-Brother movement and through the promotion of a distinct ‘Sunni vote’, they have since the early 2000s contributed towards – and benefitted from – the defence by the Reformist presidents Khatami (1997-2005) and Ruhani (since 2013) of local democracy and of the minorities’ rights. They endeavoured to help, at the same time, preventing the propagation of jihadism and Sunni radicalisation to Iran – at least until the ISIS/Daesh-claimed attacks of June 2017, in Tehran, shed light on the limits of the Islamic Republic’s strategy of reliance on Deobandi ulama and Muslim-Brother preachers in the country’s Sunni-peopled peripheries.

Simulation studies of the interactions between membrane proteins and detergents

2005 ◽  
Vol 33 (5) ◽  
pp. 910-912 ◽  
Author(s):  
P.J. Bond ◽  
J. Cuthbertson ◽  
M.S.P. Sansom
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Self Assembly ◽  
Kinetic Mechanism ◽  
Coarse Grained ◽  
Simulation Studies ◽  
High Resolution Data ◽  
Biologically Relevant ◽  
Structure And Dynamics ◽  
Detergent Interactions

Interactions between membrane proteins and detergents are important in biophysical and structural studies and are also biologically relevant in the context of folding and transport. Despite a paucity of high-resolution data on protein–detergent interactions, novel methods and increased computational power enable simulations to provide a means of understanding such interactions in detail. Simulations have been used to compare the effect of lipid or detergent on the structure and dynamics of membrane proteins. Moreover, some of the longest and most complex simulations to date have been used to observe the spontaneous formation of membrane protein–detergent micelles. Common mechanistic steps in the micelle self-assembly process were identified for both α-helical and β-barrel membrane proteins, and a simple kinetic mechanism was proposed. Recently, simplified (i.e. coarse-grained) models have been utilized to follow long timescale transitions in membrane protein–detergent assemblies.

scholarly journals Insertion of plastidic β-barrel proteins into the outer envelopes of plastids involves an intermembrane space intermediate formed with Toc75-V/OEP80

2021 ◽  
Author(s):  
Lucia E Gross ◽  
Anna Klinger ◽  
Nicole Spies ◽  
Theresa Ernst ◽  
Nadine Flinner ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Import ◽  
Membrane Insertion ◽  
Intermembrane Space ◽  
Envelope Membrane ◽  
Outer Envelope ◽  
Pea Proteins ◽  
Outer Envelope Membrane ◽  
Correct Topology ◽  
Shed Light

Abstract The insertion of organellar membrane proteins with the correct topology requires the following: First, the proteins must contain topogenic signals for translocation across and insertion into the membrane. Second, proteinaceous complexes in the cytoplasm, membrane, and lumen of organelles are required to drive this process. Many complexes required for the intracellular distribution of membrane proteins have been described, but the signals and components required for the insertion of plastidic β-barrel-type proteins into the outer membrane are largely unknown. The discovery of common principles is difficult, as only a few plastidic β-barrel proteins exist. Here, we provide evidence that the plastidic outer envelope β-barrel proteins OEP21, OEP24, and OEP37 from pea (Pisum sativum) and Arabidopsis thaliana contain information defining the topology of the protein. The information required for translocation of pea proteins across the outer envelope membrane is present within the six N-terminal β-strands. This process requires the action of TOC (translocon of the outer chloroplast membrane). After translocation into the intermembrane space, β-barrel proteins interact with TOC75-V, as exemplified by OEP37 and P39, and are integrated into the membrane. The membrane insertion of plastidic β-barrel proteins is affected by mutation of the last β-strand, suggesting that this strand contributes to the insertion signal. These findings shed light on the elements and complexes involved in plastidic β-barrel protein import.

scholarly journals Burnout in Professional Caregivers and Quality of Life in Institutionalized Center Residents

2013 ◽  
Vol 4 (1) ◽  
pp. 41-53
Author(s):  
Juan P. Martínez ◽  
Inmaculada Méndez ◽  
Esther Secanilla ◽  
Ana Benavente ◽  
Julia García Sevilla
Keyword(s):  
Quality Of Life ◽  
Ad Hoc ◽  
Maslach Burnout Inventory ◽  
The Other ◽  
People With Dementia ◽  
Professional Caregiver ◽  
The One ◽  
Shed Light ◽  
Professional Accomplishment

Starting from previous studies in professional caregivers of people with dementia and other diseases in institutionalized centers of different regions, the aim of this study was to compare burnout levels that workers present depending on the center, to create a caregiver profile with high professional accomplishment and to describe the quality of life that residents perceive Murcia and Barcelona. The instruments used were the Maslach Burnout Inventory (MBI), the Professional Caregiver Survey developed ad hoc and the Brief Questionnaire of Quality of Life (CUBRECAVI in Spanish) on residents. The results show, on the one hand, that levels of professional accomplishment may be paradoxically higher in the case of catastrophe and, on the other hand, the 98.2% of users are satisfied with the residence in which is located and 81.8% with the manner in which occupy the time. The conclusions that are extrapolated from the study shed light on the current situation of workers and residents and the influence that an earthquake can have on them.

scholarly journals FOLDING ELASTIC TRANSMEMBRANE HELICES TO FIT IN A LOW-RESOLUTION IMAGE BY ELECTRON MICROSCOPY

2011 ◽  
Vol 09 (supp01) ◽  
pp. 37-50 ◽  
Author(s):  
YUTAKA UENO ◽  
KAZUNORI KAWASAKI ◽  
OSAMU SAITO ◽  
MASAFUMI ARAI ◽  
MAKIKO SUWA
Keyword(s):  
Membrane Proteins ◽  
Structure Prediction ◽  
Molecular Model ◽  
Imaging Techniques ◽  
Transmembrane Helix ◽  
Prediction Method ◽  
Molecular Shape ◽  
Coarse Grained ◽  
Transmembrane Helices ◽  
Low Resolution

Structure prediction of membrane proteins could be constrained and thereby improved by introducing data of the observed molecular shape. We studied a coarse-grained molecular model that relied on residue-based dummy atoms to fold the transmembrane helices of a protein in the observed molecular shape. Based on the inter-residue potential, the α-helices were folded to contact each other in a simulated annealing protocol to search optimized conformation. Fitting the model into a three-dimensional volume was tested for proteins with known structures and resulted in a fairly reasonable arrangement of helices. In addition, the constraint to the packing transmembrane helix with the two-dimensional region was tested and found to work as a very similar folding guide. The obtained models nicely represented α-helices with the desired slight bend. Our structure prediction method for membrane proteins well demonstrated reasonable folding results using a low-resolution structural constraint introduced from recent cell-surface imaging techniques.

A new spectral coarse-graining algorithm based on K-means clustering in complex networks

2019 ◽  
Vol 33 (01) ◽  
pp. 1850421 ◽  
Author(s):  
Lang Zeng ◽  
Zhen Jia ◽  
Yingying Wang
Keyword(s):  
Complex Networks ◽  
Large Scale ◽  
Dynamic Properties ◽  
Coarse Graining ◽  
Kuramoto Model ◽  
Coarse Grained ◽  
Original Network ◽  
Topological Information ◽  
Real World Applications ◽  
Large Scale Networks

Coarse-graining of complex networks is one of the important algorithms to study large-scale networks, which is committed to reducing the size of networks while preserving some topological information or dynamic properties of the original networks. Spectral coarse-graining (SCG) is one of the typical coarse-graining algorithms, which can keep the synchronization ability of the original network well. However, the calculation of SCG is large, which limits its real-world applications. And it is difficult to accurately control the scale of the coarse-grained network. In this paper, a new SCG algorithm based on K-means clustering (KCSCG) is proposed, which cannot only reduce the amount of calculation, but also accurately control the size of coarse-grained network. At the same time, KCSCG algorithm has better effect in keeping the network synchronization ability than SCG algorithm. A large number of numerical simulations and Kuramoto-model example on several typical networks verify the feasibility and effectiveness of the proposed algorithm.

scholarly journals X-Mark: a benchmark for node-attributed community discovery algorithms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Salvatore Citraro ◽  
Giulio Rossetti
Keyword(s):  
State Of The Art ◽  
Graph Clustering ◽  
Clustering Methods ◽  
Community Discovery ◽  
Attributed Graphs ◽  
Node Labels ◽  
Discovery Algorithms ◽  
Shed Light

AbstractGrouping well-connected nodes that also result in label-homogeneous clusters is a task often known as attribute-aware community discovery. While approaching node-enriched graph clustering methods, rigorous tools need to be developed for evaluating the quality of the resulting partitions. In this work, we present X-Mark, a model that generates synthetic node-attributed graphs with planted communities. Its novelty consists in forming communities and node labels contextually while handling categorical or continuous attributive information. Moreover, we propose a comparison between attribute-aware algorithms, testing them against our benchmark. Accordingly to different classification schema from recent state-of-the-art surveys, our results suggest that X-Mark can shed light on the differences between several families of algorithms.

scholarly journals Isolation of Disease-relevant p53 for Cryo-Electron Microscopy Analysis

2021 ◽  
Author(s):  
Maria J. Solares ◽  
GM Jonaid ◽  
William Y. Luqiu ◽  
Yanping Liang ◽  
Madison C. Evans ◽  
...  
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
Tp53 Gene ◽  
Tumor Suppressor Protein ◽  
Protein Assemblies ◽  
Cryo Electron Microscopy ◽  
Naturally Occurring ◽  
Imaging Protocols ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis

Abstract Tumor suppressor protein TP53 (p53) plays a multi-faceted role in all cells of thehuman body. Sadly, mutations in the TP53 gene are involved in nearly ~50% of tumors,spurring erratic cell growth and disease progression. Until recently, structural informationfor p53 remained incomplete and there are limited studies on native p53 produced inhuman tumors. Here, we present a highly reproducible and effective protocol to extract,enrich, and purify native p53 protein assemblies from cancer cells for downstreamstructural studies. This method does not introduce purification tags into the p53 gene andmaintains naturally occurring modifications. In conjunction with cryo-Electron Microscopytechniques, we determined new structures for p53 monomers (~50 kDa) and tetramers(~200 kDa) at spatial resolutions of ~4.8 Å and ~7 Å, respectively.1 These modelsrevealed new insights for flexible regions of p53 along with biologically-relevantubiquitination sites. Combining biochemical and structural imaging protocols, we aim tobuild a better understanding of native p53’s impact in cancer formation.

scholarly journals The Value of Abstraction

2019 ◽  
Author(s):  
Mark K Ho ◽  
David Abel ◽  
Tom Griffiths ◽  
Michael L. Littman
Keyword(s):  
Problem Solving ◽  
Relevant Information ◽  
Scaling Up ◽  
Limited Resources ◽  
Abstract Representations ◽  
Learning Research ◽  
Crucial Ingredient ◽  
Insight Into ◽  
Shed Light

Agents that can make better use of computation, experience, time, and memory can solve a greater range of problems more effectively. A crucial ingredient for managing such finite resources is intelligently chosen abstract representations. But, how do abstractions facilitate problem solving under limited resources? What makes an abstraction useful? To answer such questions, we review several trends in recent reinforcement-learning research that provide insight into how abstractions interact with learning and decision making. During learning, abstraction can guide exploration and generalization as well as facilitate efficient tradeoffs---e.g., time spent learning versus the quality of a solution. During computation, good abstractions provide simplified models for computation while also preserving relevant information about decision-theoretic quantities. These features of abstraction are not only key for scaling up artificial problem solving, but can also shed light on what pressures shape the use of abstract representations in humans and other organisms.

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