keyword
MENU ▼
Read by QxMD icon Read
search

Conformal

keyword
https://www.readbyqxmd.com/read/28431243/cryo-em-structure-of-the-open-human-ether-%C3%A3-go-go-related-k-channel-herg
#1
Weiwei Wang, Roderick MacKinnon
The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431242/structural-and-functional-analysis-of-a-%C3%AE-2-adrenergic-receptor-complex-with-grk5
#2
Konstantin E Komolov, Yang Du, Nguyen Minh Duc, Robin M Betz, João P G L M Rodrigues, Ryan D Leib, Dhabaleswar Patra, Georgios Skiniotis, Christopher M Adams, Ron O Dror, Ka Young Chung, Brian K Kobilka, Jeffrey L Benovic
The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431169/spa-ln-a-scoring-function-of-ligand-nucleic-acid-interactions-via-optimizing-both-specificity-and-affinity
#3
Zhiqiang Yan, Jin Wang
Nucleic acids have been widely recognized as potential targets in drug discovery and aptamer selection. Quantifying the interactions between small molecules and nucleic acids is critical to discover lead compounds and design novel aptamers. Scoring function is normally employed to quantify the interactions in structure-based virtual screening. However, the predictive power of nucleic acid-ligand scoring functions is still a challenge compared to other types of biomolecular recognition. With the rapid growth of experimentally determined nucleic acid-ligand complex structures, in this work, we develop a knowledge-based scoring function of nucleic acid-ligand interactions, namely SPA-LN...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28431137/trapp-webserver-predicting-protein-binding-site-flexibility-and-detecting-transient-binding-pockets
#4
Antonia Stank, Daria B Kokh, Max Horn, Elena Sizikova, Rebecca Neil, Joanna Panecka, Stefan Richter, Rebecca C Wade
The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated workflow that allows users to explore the dynamics of a protein binding site and to detect pockets or sub-pockets that may transiently open due to protein internal motion. These transient or cryptic sub-pockets may be of interest in the design and optimization of small molecular inhibitors for a protein target of interest. The TRAPP workflow consists of the following three modules: (i) TRAPP structure- generation of an ensemble of structures using one or more of four possible molecular simulation methods; (ii) TRAPP analysis-superposition and clustering of the binding site conformations either in an ensemble of structures generated in step (i) or in PDB structures or trajectories uploaded by the user; and (iii) TRAPP pocket-detection, analysis, and visualization of the binding pocket dynamics and characteristics, such as volume, solvent-exposed area or properties of surrounding residues...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28430886/intrinsic-protein-disorder-reduces-small-scale-gene-duplicability
#5
Sanghita Banerjee, Felix Feyertag, David Alvarez-Ponce
Whereas the rate of gene duplication is relatively high, only certain duplications survive the filter of natural selection and can contribute to genome evolution. However, the reasons why certain genes can be retained after duplication whereas others cannot remain largely unknown. Many proteins contain intrinsically disordered regions (IDRs), whose structures fluctuate between alternative conformational states. Due to their high flexibility, IDRs often enable protein-protein interactions and are the target of post-translational modifications...
April 19, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28430871/cluspro-peptidock-efficient-global-docking-of-peptide-recognition-motifs-using-fft
#6
Kathryn A Porter, Bing Xia, Dmitri Beglov, Tanggis Bohnuud, Nawsad Alam, Ora Schueler-Furman, Dima Kozakov
Summary: We present an approach for the efficient docking of peptide motifs to their free receptor structures. Using a motif based search, we can retrieve structural fragments from the Protein Data Bank (PDB) that are very similar to the peptide's final, bound conformation. We use a Fast Fourier Transform (FFT) based docking method to quickly perform global rigid body docking of these fragments to the receptor. According to CAPRI peptide docking criteria, an acceptable conformation can often be found among the top-ranking predictions...
April 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28430576/ezrin-activation-by-lok-phosphorylation-involves-a-pip2-dependent-wedge-mechanism
#7
Thaher Pelaseyed, Cécile Sauvanet, Raghuvir Viswanatha, Joshua J Filter, Michael L Goldberg, Anthony Bretscher
How cells specify morphologically distinct plasma membrane domains is poorly understood. Prior work has shown that restriction of microvilli to the apical aspect of epithelial cells requires the localized activation of the membrane-F-actin linking protein ezrin. Using an in vitro system, we now define a multi-step process whereby the kinase LOK specifically phosphorylates ezrin to activate it. Binding of PIP2 to ezrin induces a conformational change permitting the insertion of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding domains of ezrin...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28430511/anti-de-sitter-particles-and-manifest-super-isometries
#8
Alex S Arvanitakis, Alec E Barns-Graham, Paul K Townsend
Starting from the classical action for a spin-zero particle in a D-dimensional anti-de Sitter (AdS) spacetime, we recover the Breitenlohner-Freedman bound by quantization. For D=4, 5, 7 and using an Sl(2;K) spinor notation for K=R,C,H, we find a bitwistor form of the action for which the AdS isometry group is linearly realized, although only for zero mass when D=4, 7 in agreement with previous constructions. For zero mass and D=4 the conformal isometry group is linearly realized. We extend these results to the superparticle in the maximally supersymmetric "AdS×S" string or M-theory vacua, showing that quantization yields a 128+128 component supermultiplet...
April 7, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28430501/metric-independence-of-vacuum-and-force-free-electromagnetic-fields
#9
Abraham I Harte
Electromagnetic fields which solve the vacuum Maxwell equations in one spacetime are well known to also be solutions in all spacetimes with conformally related metrics. This provides a sense in which electromagnetism alone cannot be used to measure certain aspects of geometry. We show that there is actually much more which cannot be so measured; relatively little of a spacetime's geometry is in fact imprinted in any particular electromagnetic field. This is demonstrated by finding a much larger class of metric transformations-involving five free functions-which preserve Maxwell solutions both in vacuum, without local currents, and also for the force-free electrodynamics associated with a tenuous plasma...
April 7, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28430446/piecing-together-the-allosteric-patterns-of-chaperonin-groel
#10
Jin Chen, Qian Zhang, Weitong Ren, Wenfei Li
Despite considerable effort, elucidating allostery of large macromolecular assemblies at a molecular level in solution remains technically challenging due to its structural complexity. Here we have employed an approach combining amide backbone hydrogen/deuterium exchange coupled with mass spectrometry, fluorescence spectroscopy and molecular simulations to characterize allosteric patterns of chaperonin GroEL, a ~800 kDa tetradecamer from E. coli. Using available crystal structures of GroEL, we quantitatively map out GroEL allosteric changes in solution by resolving exchange behaviors of 133 overlapping proteolytic peptides with more than 95% sequence coverage...
April 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28430426/the-rosetta-all-atom-energy-function-for-macromolecular-modeling-and-design
#11
Rebecca Faye Alford, Andrew Leaver-Fay, Jeliazko R Jeliazkov, Matthew J O'Meara, Frank P DiMaio, Hahnbeom Park, Maxim V Shapovalov, P Douglas Renfrew, Vikram Khipple Mulligan, Kalli Kappel, Jason W Labonte, Michael Steven Pacella, Richard Bonneau, Philip Bradley, Roland L Dunbrack, Rhiju Das, David Baker, Brian Kuhlman, Tanja Kortemme, Jeffrey J Gray
Over the past decade, the Rosetta biomolecular modeling suite has informed diverse biological questions and engineering challenges ranging from interpretation of low-resolution structural data to design of nanomaterials, protein therapeutics, and vaccines. Central to Rosetta's success is the energy function: a model parameterized from small molecule and X-ray crystal structure data used to approximate the energy associated with each biomolecule conformation. This paper describes the mathematical models and physical concepts that underlie the latest Rosetta Energy Function, REF15...
April 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28430399/targeting-conformational-activation-of-cdk2-kinase
#12
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris
Cyclin-dependent kinases constitute attractive pharmacological targets for cancer therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of the CDK and therefore suffer from limited selectivity and emergence of resistance. The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation...
April 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28429939/solute-rotation-in-ionic-liquids-size-shape-and-electrostatic-effects
#13
Christopher A Rumble, Caleb Uitvlugt, Brian Conway, Mark Maroncelli
Herein are reported temperature-dependent measurements and molecular dynamics simulations designed to investigate the effects of molecular size, shape, and electrostatics on rotational dynamics in ionic liquids. Experiments were performed in the representative ionic liquid 1-butyl-3-methylimadazolium tetrafluoroborate ([Im41][BF4]) and simulations in the generic ionic liquid model ILM2 as well as a more detailed representation of [Im41][BF4]. 2H longitudinal spin relaxation times were measured for deuterated versions of 1,4-dimethylbenzene, 1-cyano-4-methylbenzene, and 1,4-dimethylpyridinium between 296-337 K...
April 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28429870/induction-of-axial-chirality-in-8-arylquinolines-via-halogenation-reactions-using-bifunctional-organocatalysts
#14
Ryota Miyaji, Keisuke Asano, Seijiro Matsubara
The enantioselective syntheses of axially chiral heterobiaryls were accomplished via the aromatic electrophilic halogenation of 3-(quinolin-8-yl)phenols using bifunctional organocatalysts, which control the molecular conformations during successive halogenations. Axially chiral quinoline derivatives, which have rarely been synthesized in an enantioselective catalytic manner, were afforded in moderate-to-good enantioselectivities via bromination, and an analogous protocol also enabled enantioselective iodination...
April 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28429788/the-hsp90-chaperone-machinery
#15
REVIEW
Florian H Schopf, Maximilian M Biebl, Johannes Buchner
The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells. As HSP90 has several hundred protein substrates (or 'clients'), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease. A large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients...
April 21, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28429757/soft-electronics-enabled-ergonomic-human-computer-interaction-for-swallowing-training
#16
Yongkuk Lee, Benjamin Nicholls, Dong Sup Lee, Yanfei Chen, Youngjae Chun, Chee Siang Ang, Woon-Hong Yeo
We introduce a skin-friendly electronic system that enables human-computer interaction (HCI) for swallowing training in dysphagia rehabilitation. For an ergonomic HCI, we utilize a soft, highly compliant ("skin-like") electrode, which addresses critical issues of an existing rigid and planar electrode combined with a problematic conductive electrolyte and adhesive pad. The skin-like electrode offers a highly conformal, user-comfortable interaction with the skin for long-term wearable, high-fidelity recording of swallowing electromyograms on the chin...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429370/the-role-of-charged-residues-in-independent-glycine-receptor-folding-domains-for-intermolecular-interactions-and-ion-channel-function
#17
Georg Langlhofer, Carmen Villmann
Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented in patients suffering from hyperekplexia and in the mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains the TM3-4 loop, TM4, and C-terminal sequences is essential for pentameric receptor arrangements. In vitro coexpressions of GlyRα1 truncated N-domains and C- domains were able to restore ion channel function. An ionic interaction between both domains was hypothesised as the underlying mechanism...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28429219/effects-of-different-modes-of-hypobaric-hypoxia-on-the-content-of-epigenetic-factors-in-the-rat-in-neurons-of-rat-neocortex
#18
M O Samoilov, A V Churilova, T S Glushchenko, E A Rybnikova
We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28429077/-implementation-of-the-german-s3-guidelines-on-dementia-in-clinical-practice-wish-or-reality
#19
H Lohmann, F Kulessa, H Holling, A Johnen, S Reul, G Lueg, T Duning
BACKGROUND: Published in 2009, the German S3 guidelines on dementia define a milestone in quality improvement of the diagnostics and treatment of dementia. In clinical practice patients suffering from dementia are primarily treated by physicians in private practice; therefore, this study examined how the guidelines are implemented in outpatient clinical settings. Furthermore, it aimed at the identification of behavioral determinants that govern the actual diagnostic and therapeutic approach in clinical practice...
April 20, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28429063/direct-fluorescence-anisotropy-assay-for-cocaine-using-tetramethylrhodamine-labeled-aptamer
#20
Yingxiong Liu, Qiang Zhao
Development of simple, sensitive, and rapid method for cocaine detection is important in medicine and drug abuse monitoring. Taking advantage of fluorescence anisotropy and aptamer, this study reports a direct fluorescence anisotropy (FA) assay for cocaine by employing an aptamer probe with tetramethylrhodamine (TMR) labeled on a specific position. The binding of cocaine and the aptamer causes a structure change of the TMR-labeled aptamer, leading to changes of the interaction between labeled TMR and adjacent G bases in aptamer sequence, so FA of TMR varies with increasing of cocaine...
April 20, 2017: Analytical and Bioanalytical Chemistry
keyword
keyword
109766
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"