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Single molecule biophysics

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https://www.readbyqxmd.com/read/28538142/an-introduction-to-infinite-hmms-for-single-molecule-data-analysis
#1
REVIEW
Ioannis Sgouralis, Steve Pressé
The hidden Markov model (HMM) has been a workhorse of single-molecule data analysis and is now commonly used as a stand-alone tool in time series analysis or in conjunction with other analysis methods such as tracking. Here, we provide a conceptual introduction to an important generalization of the HMM, which is poised to have a deep impact across the field of biophysics: the infinite HMM (iHMM). As a modeling tool, iHMMs can analyze sequential data without a priori setting a specific number of states as required for the traditional (finite) HMM...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28529337/dynamic-chromatin-technologies-from-individual-molecules-to-epigenomic-regulation-in-cells
#2
REVIEW
Olivier Cuvier, Beat Fierz
The establishment and maintenance of chromatin states involves multiscale dynamic processes integrating transcription factor and multiprotein effector dynamics, cycles of chemical chromatin modifications, and chromatin structural organization. Recent developments in genomic technologies are emerging that are enabling a view beyond ensemble- and time-averaged properties and are revealing the importance of dynamic chromatin states for cell fate decisions, differentiation and reprogramming at the single-cell level...
May 22, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28505809/dissociation-rates-from-single-molecule-pulling-experiments-under-large-thermal-fluctuations-or-large-applied-force
#3
Masoud Abkenar, Thomas H Gray, Alessio Zaccone
Theories that are used to extract energy-landscape information from single-molecule pulling experiments in biophysics are all invariably based on Kramers' theory of the thermally activated escape rate from a potential well. As is well known, this theory recovers the Arrhenius dependence of the rate on the barrier energy and crucially relies on the assumption that the barrier energy is much larger than k_{B}T (limit of comparatively low thermal fluctuations). As was shown already in Dudko et al. [Phys. Rev...
April 2017: Physical Review. E
https://www.readbyqxmd.com/read/28489428/a-single-molecule-view-of-genome-editing-proteins-biophysical-mechanisms-for-tales-and-crispr-cas9
#4
Luke Cuculis, Charles M Schroeder
Exciting new advances in genome engineering have unlocked the potential to radically alter the treatment of human disease. In this review, we discuss the application of single-molecule techniques to uncover the mechanisms behind two premier classes of genome editing proteins: transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have facilitated a striking number of gene editing applications in a variety of organisms; however, we are only beginning to understand the molecular mechanisms governing the DNA editing properties of these systems...
May 10, 2017: Annual Review of Chemical and Biomolecular Engineering
https://www.readbyqxmd.com/read/28482279/improving-certainty-in-single-molecule-imaging
#5
REVIEW
John Sh Danial, Ana J García-Sáez
The spatiotemporal organization of biological entities and the complex network of interactions they sponsor has proven challenging to visualize. Modern biophysics has brought a wealth of techniques for probing cellular structure and dynamics of which fluorescence-based single molecule detection has emerged as a powerful tool. In this review, we summarize notable breakthroughs in biological research based on single molecule imaging, identify prevailing shortcomings in single molecule detection and present current opinion on ameliorating some of its limitations for wider applicability...
May 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28448574/fusion-expression-of-occludin-extracellular-loops-and-an-%C3%AE-helical-bundle-a-new-research-model-for-tight-junction
#6
Xiaojing Chi, Xia Zhao, Wei Wang, Yuqiang Niu, Min Cheng, Xiuying Liu, Sheng Cui, Wei Yang
Tight junctions (TJs) are the outermost structures of intercellular junctions and are highly specialized membrane domains involved in many important cellular processes. However, most TJ proteins are four-time transmembrane proteins and are difficult to express in their correct soluble form, which limits their functional study and therapeutic application. Human occludin (OCLN) is a major component of TJs and an essential co-receptor for hepatitis C virus (HCV) cell entry. To explore expression strategy for recombinant TJ proteins possessing integrated and functional extracellular loops, OCLN was here used as a model molecule, and several prokaryotic fusion constructs were designed by docking OCLN extracellular loops (ECLs) to HIV-1 gp41 NHR and CHR six-helical bundle (6HV1); then their biophysical features and anti-HCV activity were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28435614/time-resolved-biophysical-approaches-to-nucleocytoplasmic-transport
#7
REVIEW
Francesco Cardarelli
Molecules are continuously shuttling across the nuclear envelope barrier that separates the nucleus from the cytoplasm. Instead of being just a barrier to diffusion, the nuclear envelope is rather a complex filter that provides eukaryotes with an elaborate spatiotemporal regulation of fundamental molecular processes, such as gene expression and protein translation. Given the highly dynamic nature of nucleocytoplasmic transport, during the past few decades large efforts were devoted to the development and application of time resolved, fluorescence-based, biophysical methods to capture the details of molecular motion across the nuclear envelope...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28434999/smfret-experiments-of-the-rna-polymerase-ii-transcription-initiation-complex
#8
REVIEW
Nicole Malkusch, Thilo Dörfler, Julia Nagy, Tobias Eilert, Jens Michaelis
Single-molecule fluorescence and in particular single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful tool to provide real-time information on the dynamic architecture of large macromolecular structures such as eukaryotic transcription initiation complexes. In contrast to other structural biology methods, not only structural details, but dynamics transitions are revealed thus closing in on the underlying molecular mechanisms. Here, we describe a comprehensive quantitative biophysical toolbox which can be used for rigorous analysis of dynamic protein-nucleic acid complexes and is applied to the study of eukaryotic transcription initiation...
April 19, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28424742/fret-from-single-to-multiplexed-signaling-events
#9
REVIEW
Gertrude Bunt, Fred S Wouters
Förster resonance energy transfer (FRET) is a powerful tool for the visualization of molecular signaling events such as protein activities and interactions in cells. In its different implementations, FRET microscopy has been mainly used for monitoring single events. Recently, there has been a trend of extending FRET imaging towards the simultaneous detection of multiple events and interactions. The concomitant increase in experimental complexity requires a deeper understanding of the biophysical background of FRET...
April 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28424741/catalytic-robustness-and-torque-generation-of-the-f1-atpase
#10
REVIEW
Hiroyuki Noji, Hiroshi Ueno, Duncan G G McMillan
The F1-ATPase is the catalytic portion of the FoF1 ATP synthase and acts as a rotary molecular motor when it hydrolyzes ATP. Two decades have passed since the single-molecule rotation assay of F1-ATPase was established. Although several fundamental issues remain elusive, basic properties of F-type ATPases as motor proteins have been well characterized, and a large part of the reaction scheme has been revealed by the combination of extensive structural, biochemical, biophysical, and theoretical studies. This review is intended to provide a concise summary of the fundamental features of F1-ATPases, by use of the well-described model F1 from the thermophilic Bacillus PS3 (TF1)...
April 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28414321/an-orthogonal-single-molecule-experiment-reveals-multiple-attempt-dynamics-of-type-ia-topoisomerases
#11
Kathryn H Gunn, John F Marko, Alfonso Mondragón
Topoisomerases are enzymes that are involved in maintaining the topological state of cellular DNA. Their dynamic characteristics remain poorly understood despite numerous structural, biophysical and biochemical studies. Recent single-molecule experiments revealed that an important feature of the type IA topoisomerase mechanism is the presence of pauses between relaxation events. However, these experiments could not determine whether the protein remains DNA bound during the pauses or what relationship may exist between protein domain movements and topological changes in the DNA...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28406920/experimental-and-mathematical-analysis-of-camp-nanodomains
#12
Christian Lohse, Andreas Bock, Isabella Maiellaro, Annette Hannawacker, Lothar R Schad, Martin J Lohse, Wolfgang R Bauer
In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28375735/single-molecule-studies-of-telomeres-and-telomerase
#13
Joseph W Parks, Michael D Stone
Telomeres are specialized chromatin structures that protect chromosome ends from dangerous processing events. In most tissues, telomeres shorten with each round of cell division, placing a finite limit on cell growth. In rapidly dividing cells, including the majority of human cancers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length. The dynamic properties of telomeres and telomerase render them difficult to study using ensemble biochemical and structural techniques...
March 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28375733/single-molecule-analysis-of-bacterial-dna-repair-and-mutagenesis
#14
Stephan Uphoff, David J Sherratt
Ubiquitous conserved processes that repair DNA damage are essential for the maintenance and propagation of genomes over generations. Then again, inaccuracies in DNA transactions and failures to remove mutagenic lesions cause heritable genome changes. Building on decades of research using genetics and biochemistry, unprecedented quantitative insight into DNA repair mechanisms has come from the new-found ability to measure single proteins in vitro and inside individual living cells. This has brought together biologists, chemists, engineers, physicists, and mathematicians to solve longstanding questions about the way in which repair enzymes search for DNA lesions and form protein complexes that act in DNA repair pathways...
March 24, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28368824/monte-carlo-analysis-of-molecule-absorption-probabilities-in-diffusion-based-nanoscale-communication-systems-with-multiple-receivers
#15
Dogu Arifler, Dizem Arifler
For biomedical applications of nanonetworks, employing molecular communication for information transport is advantageous over nano-electromagnetic communication: molecular communication is potentially biocompatible and inherently energy-efficient. Recently, several studies have modeled receivers in diffusion-based molecular communication systems as "perfectly monitoring" or "perfectly absorbing" spheres based on idealized descriptions of chemoreception. In this work, we focus on perfectly absorbing receivers and present methods to improve the accuracy of simulation procedures that are used to analyze these receivers...
March 27, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28350161/multiparametric-atomic-force-microscopy-imaging-of-biomolecular-and-cellular-systems
#16
David Alsteens, Daniel J Müller, Yves F Dufrêne
There is a need in biochemical research for new tools that can image and manipulate biomolecular and cellular systems at the nanoscale. During the past decades, there has been tremendous progress in developing atomic force microscopy (AFM) techniques to analyze biosystems, down to the single-molecule level. Force-distance (FD) curve-based AFM in particular has enabled researchers to map and quantify biophysical properties and biomolecular interactions on a wide variety of specimens. Despite its great potential, this AFM method has long been limited by its low spatial and temporal resolutions...
March 28, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28341438/engineering-a-novel-porin-ompgf-via-strand-replacement-from-computational-analysis-of-sequence-motif
#17
Meishan Lin, Ge Zhang, Monifa Fahie, Leslie K Morgan, Min Chen, Timothy A Keiderling, Linda J Kenney, Jie Liang
β-Barrelmembrane proteins (βMPs) form barrel-shaped pores in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Because of the robustness of their barrel structures, βMPs have great potential as nanosensors for single-molecule detection. However, natural βMPs currently employed have inflexible biophysical properties and are limited in their pore geometry, hindering their applications in sensing molecules of different sizes and properties. Computational engineering has the promise to generate βMPs with desired properties...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28337984/lipid-dependent-conformational-dynamics-underlie-the-functional-versatility-of-t-cell-receptor
#18
Xingdong Guo, Chengsong Yan, Hua Li, Wenmao Huang, Xiaoshan Shi, Min Huang, Yingfang Wang, Weiling Pan, Mingjun Cai, Lunyi Li, Wei Wu, Yibing Bai, Chi Zhang, Zhijun Liu, Xinyan Wang, Xiaohui F Zhang, Chun Tang, Hongda Wang, Wanli Liu, Bo Ouyang, Catherine C Wong, Yi Cao, Chenqi Xu
T-cell receptor-CD3 complex (TCR) is a versatile signaling machine that can initiate antigen-specific immune responses based on various biochemical changes of CD3 cytoplasmic domains, but the underlying structural basis remains elusive. Here we developed biophysical approaches to study the conformational dynamics of CD3ε cytoplasmic domain (CD3εCD). At the single-molecule level, we found that CD3εCD could have multiple conformational states with different openness of three functional motifs, i.e., ITAM, BRS and PRS...
April 2017: Cell Research
https://www.readbyqxmd.com/read/28324509/human-telomeric-g-quadruplex-structures-and-g-quadruplex-interactive-compounds
#19
Clement Lin, Danzhou Yang
G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures, and the human telomeric DNA G-quadruplexes are considered attractive targets for anticancer drugs. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method in determining the G-quadruplex structures under physiologically relevant conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315749/integrated-structural-biology-to-unravel-molecular-mechanisms-of-protein-rna-recognition
#20
REVIEW
Andreas Schlundt, Jan-Niklas Tants, Michael Sattler
Recent advances in RNA sequencing technologies have greatly expanded our knowledge of the RNA landscape in cells, often with spatiotemporal resolution. These techniques identified many new (often non-coding) RNA molecules. Large-scale studies have also discovered novel RNA binding proteins (RBPs), which exhibit single or multiple RNA binding domains (RBDs) for recognition of specific sequence or structured motifs in RNA. Starting from these large-scale approaches it is crucial to unravel the molecular principles of protein-RNA recognition in ribonucleoprotein complexes (RNPs) to understand the underlying mechanisms of gene regulation...
March 16, 2017: Methods: a Companion to Methods in Enzymology
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