40,743 results match your criteria conformational changes

Modelling the adsorption of proteins to nanoparticles at the solid-liquid interface.

J Colloid Interface Sci 2021 Jul 22;605:286-295. Epub 2021 Jul 22.

School of Life Sciences, University of Lincoln, Lincoln LN6 7TS, UK. Electronic address:

Hypothesis: We developed a geometrical model to determine the theoretical maximum number of proteins that can pack as a monolayer surrounding a spherical nanoparticle. We applied our new model to study the adsorption of receptor binding domain (RBD) of the SARS-CoV-2 spike protein to silica nanoparticles. Due to its abundance and extensive use in manufacturing, silica represents a reservoir where the virus can accumulate. Read More

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Mechanisms of HCV resistance to broadly neutralizing antibodies.

Curr Opin Virol 2021 Jul 27;50:23-29. Epub 2021 Jul 27.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address:

Broadly neutralizing antibodies (bNAbs) block infection by genetically diverse hepatitis C virus (HCV) isolates by targeting relatively conserved epitopes on the HCV envelope glycoproteins, E1 and E2. Many amino acid substitutions conferring resistance to these bNAbs have been characterized, identifying multiple mechanisms of bNAb escape. Some resistance substitutions follow the expected mechanism of directly disrupting targeted epitopes. Read More

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A novel vision into the binding behavior of curcumin with human serum albumin-holo transferrin complex: molecular dynamic simulation and multi-spectroscopic perspectives.

J Biomol Struct Dyn 2021 Jul 30:1-19. Epub 2021 Jul 30.

Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

In this work, we investigated the simultaneous binding of curcumin (CUR) to human serum albumin (HSA) and human-holo transferrin (HTF) in the roles of binary and ternary systems. The binding affinity and binding site of protein-protein interaction were studied by the methods of multiple spectroscopic and molecular dynamics (MD) simulation. According to the results, the measurements for binding constant of HSA-CUR, HTF-CUR and (HSA-HTF) CUR complexes were observed to be 1. Read More

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Exploring Post-activation Conformational Changes in Pigeon Cryptochrome 4.

J Phys Chem B 2021 Jul 30. Epub 2021 Jul 30.

Department of Physics, Carl von Ossietzky Universät Oldenburg, Carl-von-Ossietzky Str. 9-11, Oldenburg 26129, Germany.

A widespread hypothesis ascribes the ability of migratory birds to navigate over large distances to an inclination compass realized by the protein cryptochrome in the birds' retinae. Cryptochromes are activated by blue light, which induces a radical pair state, the spin dynamics of which may become sensitive to earth's weak magnetic fields. The magnetic information is encoded and passed on to downstream processes by structural rearrangements of the protein, the details of which remain vague. Read More

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[Ligands of TetR family transcriptional regulators: a review].

Sheng Wu Gong Cheng Xue Bao 2021 Jul;37(7):2379-2392

Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, Anhui, China.

TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control target gene expression. Read More

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Kinetic Evidence for an Induced Fit Mechanism in the Binding of the Substrate Camphor by Cytochrome P450.

ACS Catal 2021 Jan 29;11(2):639-649. Epub 2020 Dec 29.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States.

Bacterial cytochrome P450 (P450) 101A1 (P450) has served as a prototype among the P450 enzymes and has high catalytic activity towards its cognate substrate, camphor. X-ray crystallography and NMR and IR spectroscopy have demonstrated the existence of multiple conformations of many P450s, including P450. Kinetic studies have indicated that substrate binding to several P450s is dominated by a conformational selection process, in which the substrate binds an individual conformer(s) of the unliganded enzyme. Read More

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January 2021

Structural Deformation of MTX Induced by Nanodrug Conjugation Dictate Intracellular Drug Transport and Drug Efficacy.

Int J Nanomedicine 2021 22;16:4943-4957. Epub 2021 Jul 22.

Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea.

Background: Understanding structural interactions between the active drug and conjugated nanoparticles is critical for optimizing intracellular drug transport and for increasing nano drug efficacy. In this regard, analyzing the conformational deformation of conjugated drugs surrounding nanoparticles is essential to understand the corresponding nanodrug efficacy.

Purpose: The objective of this study is to present an optimal synthesis method for efficient drug delivery through a clear structural analysis of nanodrugs according to the type of conjugation. Read More

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Deep learning-based mixed-dimensional Gaussian mixture model for characterizing variability in cryo-EM.

Nat Methods 2021 Jul 29. Epub 2021 Jul 29.

Verna Marrs and McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA.

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging. Read More

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Three-color single-molecule imaging reveals conformational dynamics of dynein undergoing motility.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

HHMI, University of California, San Francisco, CA 94158;

The motor protein dynein undergoes coordinated conformational changes of its domains during motility along microtubules. Previous single-molecule studies analyzed the motion of the AAA rings of the dynein homodimer, but not the distal microtubule-binding domains (MTBDs) that step along the track. Here, we simultaneously tracked with nanometer precision two MTBDs and one AAA ring of a single dynein as it underwent hundreds of steps using three-color imaging. Read More

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Transient Electric Birefringence of Linear and Circular DNA: A Comparison of Kinetic Theory Predictions.

J Phys Chem B 2021 Jul 29. Epub 2021 Jul 29.

Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544, United States.

The use of monodisperse DNA and restriction enzyme modification allows the preparation of model samples of polymer rings and linear chains with a precision that is not possible by conventional synthetic routes. These samples allow direct comparisons of the predictions of polymer kinetic theories. Transient electric birefringence allows rapid imposition or forces (∼100 ns) and monitoring of conformational changes (∼0. Read More

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Chemical Reduction of Ni Cyclam and Characterization of Isolated Ni Cyclam with Cryogenic Vibrational Spectroscopy and Inert-Gas-Mediated High-Resolution Mass Spectrometry.

J Phys Chem A 2021 Jul 29. Epub 2021 Jul 29.

Sterling Chemistry Laboratory, Chemistry Department, Yale University, New Haven, Connecticut 06520, United States.

Ni cyclam (cyclam = 1,4,8,11-tetraazacyclotetradecane) is an efficient catalyst for the selective reduction of CO to CO. A crucial elementary step in the proposed catalytic cycle is the coordination of CO to a Ni cyclam intermediate. Isolation and spectroscopic characterization of this labile Ni species without solvent has proven to be challenging, however, and only partial IR spectra have previously been reported using multiple photon fragmentation of ions generated by gas-phase electron transfer to the Ni cyclam dication at 300 K. Read More

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Tyrosine -GalNAc Alters the Conformation and Proteolytic Susceptibility of APP Model Glycopeptides.

ACS Chem Neurosci 2021 Jul 29. Epub 2021 Jul 29.

Department of Chemistry and Biochemistry, Charles E, Schmidt College of Science, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431, United States.

The amyloid-β precursor protein (APP) undergoes proteolytic cleavage by α-, β-, and γ-secretases, to determine its fate in Alzheimer's disease (AD) pathogenesis. Recent findings suggest a possible role of -glycosylation in APP's proteolytic processing. Therefore, we synthesized native and Swedish-double-mutated APP (glyco)peptides with Tyr--GalNAc. Read More

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Charge-transfer electronic states in organic solar cells: a TDDFT study.

Phys Chem Chem Phys 2021 Jul 29. Epub 2021 Jul 29.

Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán, CDMX 04510, Mexico.

The prediction of new organic photovoltaic materials in organic solar cells (OSCs) must include a precise description of charge-transfer states because they are involved in electron-transfer processes such as charge separation and charge recombination which govern the device efficiency. Also, as the experimental performance of an optoelectronic device is measured for nonequilibrium nanostructures, computational approaches need models that can incorporate morphology effects. Usually, this aspect is treated by molecular dynamics simulation (MDS) methodologies; however, methodologies and formalisms to calculate the electron-transfer processes are still controversial and sometimes do not connect their information with the phase morphologies. Read More

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Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity.

Front Cell Infect Microbiol 2021 12;11:604511. Epub 2021 Jul 12.

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, United States.

Bacterial small RNAs (sRNAs) are critical post-transcriptional regulators that exert broad effects on cell physiology. One class of sRNAs, referred to as -acting sRNAs, base-pairs with mRNAs to cause changes in their stability or translation. Another class of sRNAs sequesters RNA-binding proteins that in turn modulate mRNA expression. Read More

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Allosteric Inhibition of a Vesicular Glutamate Transporter by an Isoform-Specific Antibody.

Biochemistry 2021 Jul 28. Epub 2021 Jul 28.

Departments of Neurology and Physiology, UCSF School of Medicine, 600 16th Street, San Francisco, California 94143, United States.

The role of glutamate in excitatory neurotransmission depends on its transport into synaptic vesicles by the vesicular glutamate transporters (VGLUTs). The three VGLUT isoforms exhibit a complementary distribution in the nervous system, and the knockout of each produces severe, pleiotropic neurological effects. However, the available pharmacology lacks sensitivity and specificity, limiting the analysis of both transport mechanism and physiological role. Read More

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DNA binding alters ARv7 dimer interactions.

J Cell Sci 2021 Jul 28;134(14). Epub 2021 Jul 28.

School of Medicine, Koç University, Istanbul 34450, Turkey.

Androgen receptor (AR) splice variants are proposed to be a potential driver of lethal castration-resistant prostate cancer. AR splice variant 7 (ARv7) is the most commonly observed isoform and strongly correlates with resistance to second-generation anti-androgens. Despite this clinical evidence, the interplay between ARv7 and the highly expressed full-length AR (ARfl) remains unclear. Read More

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The synergistic mechanisms of apo-ferritin structural transitions and Au(III) ion transportation: molecular dynamics simulations with the Markov state model.

Phys Chem Chem Phys 2021 Jul 27. Epub 2021 Jul 27.

State Key Lab of Chemical Engineering, Ministry of Science and Technology; Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.

Due to its unique structure, recent years have witnessed the use of apo-ferritin to accumulate various non-natural metal ions as a scaffold for nanomaterial synthesis. However, the transport mechanism of metal ions into the cavity of apo-ferritin is still unclear, limiting the rational design and controllable preparation of nanomaterials. Here, we conducted all-atom classical molecular dynamics (MD) simulations combined with Markov state models (MSMs) to explore the transportation behavior of Au(iii) ions. Read More

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Protonation states at different pH, conformational changes and impact of glycosylation in synapsin Ia.

Phys Chem Chem Phys 2021 Jul 28. Epub 2021 Jul 28.

H.E.J., Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. and Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

Synapsin I (SynI) is the most abundant brain phosphoprotein present at presynaptic terminals that regulates neurotransmitter release, clustering of synaptic vesicles (SVs) at active zones, and stimulates synaptogenesis and neurite outgrowth. Earlier studies have established that SynI displays pH-dependent tethering of SVs to actin filaments and exhibits a maximum binding around neutral pH, however, the effect of pH shift from acidic to basic on the conformational stability of SynI has not been explored yet. Another important aspect of SynIa is its O-GlcNAcylation (O-GlcNac) at the Thr87 position, which is responsible for the positive regulation of synaptic plasticity linked to learning and memory in mice. Read More

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Huntington disease: Advances in the understanding of its mechanisms.

Clin Park Relat Disord 2020 6;3:100056. Epub 2020 May 6.

National Administration of Laboratories and Institutes of Health, ANLIS, Dr. Carlos G. Malbrán, Argentina.

Huntington disease (HD) is a devastating monogenic autosomal dominant disorder. HD is caused by a CAG expansion in exon 1 of the gene coding for huntingtin, placed in the short arm of chromosome 4. Despite its well-defined genetic origin, the molecular and cellular mechanisms underlying the disease are unclear and complex. Read More

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Dynamics of Germination Behaviour, Protein Secondary Structure, Technofunctional Properties, Antinutrients, Antioxidant Capacity and Mineral Elements in Germinated Dhaincha.

Food Technol Biotechnol 2021 Jun;59(2):238-250

Department of Food Science and Technology, Punjab Agricultural University, Ludhiana-141004 (Punjab), India.

Research Background: Dhaincha () is a forage legume primarily used for green manuring and animal feed. Good nutritional profile of dhaincha makes it a potential alternative legume in human nutrition. However, the presence of high amount of antinutrients poses a problem in its utilisation for food applications. Read More

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Structural basis for genome packaging, retention, and ejection in human cytomegalovirus.

Nat Commun 2021 07 27;12(1):4538. Epub 2021 Jul 27.

Cryo-Electron Microscopy Research Center, the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

How the human cytomegalovirus (HCMV) genome-the largest among human herpesviruses-is packaged, retained, and ejected remains unclear. We present the in situ structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV. The 5-fold symmetric 10-helix anchor-uncommon among known portals-contacts the portal-encircling DNA, which is presumed to squeeze the portal as the genome packaging proceeds. Read More

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Mol Pharmacol 2021 Jul 27. Epub 2021 Jul 27.

Imperial College London, United Kingdom

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor and mainstay therapeutic target for the treatment of type 2 diabetes and obesity. Recent reports have highlighted how biased agonism at the GLP-1R affects sustained glucose-stimulated insulin secretion through avoidance of desensitisation and downregulation. A number of GLP-1R agonists (GLP-1RAs) feature a fatty acid moiety to prolong their pharmacokinetics via increased albumin binding, but the potential for these chemical changes to influence GLP-1R function has rarely been investigated beyond potency assessments for cyclic adenosine monophosphate (cAMP). Read More

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Structural modelling of SARS-CoV-2 new variant (B.1.1.7) suggests enhanced furin binding and infectivity.

Virus Res 2021 Jul 24:198522. Epub 2021 Jul 24.

Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait.

The B.1.1. Read More

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Nonmuscle Myosin II Regulation Directs Its Multiple Roles in Cell Migration and Division.

Annu Rev Cell Dev Biol 2021 Jul 27. Epub 2021 Jul 27.

Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas, University of Salamanca, 37007 Salamanca, Spain; email:

Nonmuscle myosin II (NMII) is a multimeric protein complex that generates most mechanical force in eukaryotic cells. NMII function is controlled at three main levels. The first level includes events that trigger conformational changes that extend the complex to enable its assembly into filaments. Read More

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The Induction Mechanism of the Flavonoid-Responsive Regulator FrrA.

FEBS J 2021 Jul 27. Epub 2021 Jul 27.

Institute for Biochemistry, Dept. Molecular Structural Biology, University of Greifswald, Greifswald, Germany.

Bradyrhizobium diazoefficiens, a bacterial symbiont of soybean and other leguminous plants, enters a nodulation-promoting genetic programme in the presence of host-produced flavonoids and related signalling compounds. Here, we describe the crystal structure of an isoflavonoid-responsive regulator (FrrA) from Bradyrhizobium, as well as co-crystal structures with inducing and non-inducing ligands (genistein and naringenin, respectively). The structures reveal a TetR-like fold whose DNA-binding domain is capable of adopting a range of orientations. Read More

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Emergence of directional bias in tau deposition from axonal transport dynamics.

PLoS Comput Biol 2021 Jul 27;17(7):e1009258. Epub 2021 Jul 27.

Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, California, United States of America.

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer's disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. Read More

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The denatured state of HIV-1 protease under native conditions.

Proteins 2021 Jul 27. Epub 2021 Jul 27.

Department of Physics, Università degli Studi di Milano, via Celoria 16, Milan, Italy.

The denatured state of several proteins has been shown to display transient structures that are relevant for folding, stability and aggregation. To detect them by nuclear magnetic resonance (NMR) spectroscopy, the denatured state must be stabilized by chemical agents or changes in temperature. This makes the environment different from that experienced in biologically relevant processes. Read More

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Molecular insights into the human ABCB6 transporter.

Cell Discov 2021 Jul 27;7(1):55. Epub 2021 Jul 27.

Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.

ABCB6 plays a crucial role in energy-dependent porphyrin transport, drug resistance, toxic metal resistance, porphyrin biosynthesis, protection against stress, and encoding a blood group system Langereis antigen. However, the mechanism underlying porphyrin transport is still unclear. Here, we determined the cryo-electron microscopy (cryo-EM) structures of nanodisc-reconstituted human ABCB6 trapped in an apo-state and an ATP-bound state at resolutions of 3. Read More

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Recognition and binding of FEZ-1 from Legionella with penicillin V and cefoxitin by fluorescence spectra in combination with molecular dynamics simulation.

Enzyme Microb Technol 2021 Sep 7;149:109819. Epub 2021 May 7.

College of Life Science, Northwest University, Xi'an, 710069, China. Electronic address:

The recognition and interaction of FEZ-1 from Legionella (FEZ-1) with penicillin V(PV) and cefoxitin(CFX) were investigated using fluorescence spectra in combination with molecular dynamics simulation (MD). The results revealed that the CFX bind with FEZ-1 in stronger interaction and induced larger conformational change than PV, despite all being forced by the electrostatic interaction and along with the changing in an environment of amino acid residues as well as the polypeptide skeleton inside the FEZ-1. Moreover, only the loop1, loop2, and N-terminal were observed locating near the binding pocket of FEZ-1, consisting of a flexible "gate-like" zone with better adaptability that controlled the entrance of antibiotic into the pocket by allowing the newly introduced antibiotic to match the pocket better through the conformational changes of these three substructures in the binding procedure. Read More

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September 2021

Structural Decoding of a Small Molecular Inhibitor on the Binding of SARS-CoV-2 to the ACE 2 Receptor.

J Phys Chem B 2021 Jul 23. Epub 2021 Jul 23.

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh 175005, India.

Inhibition of the interaction of the receptor-binding domain (RBD) of the spike protein and the human angiotensin-converting enzyme 2 (ACE 2) receptor is the most effective therapeutic formulation to restrict the contagious respiratory illness and multiple organ failure caused by the novel SARS-CoV-2 virus. Based on the structural decoding of the RBD of the spike protein, here we have generated a new set of small molecules that have strong inhibiting properties on the binding of the spike protein to ACE 2 receptors. These small-molecule inhibitors surprisingly show binding to the main protease, nucleoprotein, and RNA-dependent RNA polymerase, which are the other responsible factors for the viral infection. Read More

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