284 results match your criteria Annual Review Of Biophysics[Journal]


Nonequilibrium Thermodynamics in Cell Biology: Extending Equilibrium Formalism to Cover Living Systems.

Annu Rev Biophys 2020 May;49:227-246

Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, USA; email:

We discuss new developments in the nonequilibrium dynamics and thermodynamics of living systems, giving a few examples to demonstrate the importance of nonequilibrium thermodynamics for understanding biological dynamics and functions. We study single-molecule enzyme dynamics, in which the nonequilibrium thermodynamic and dynamic driving forces of chemical potential and flux are crucial for the emergence of non-Michaelis-Menten kinetics. We explore single-gene expression dynamics, in which nonequilibrium dissipation can suppress fluctuations. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081656DOI Listing

Milestoning: An Efficient Approach for Atomically Detailed Simulations of Kinetics in Biophysics.

Authors:
Ron Elber

Annu Rev Biophys 2020 May;49:69-85

Oden Institute for Computational Engineering and Sciences, Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, USA; email:

Recent advances in theory and algorithms for atomically detailed simulations open the way to the study of the kinetics of a wide range of molecular processes in biophysics. The theories propose a shift from the traditionally very long molecular dynamic trajectories, which are exact but may not be efficient in the study of kinetics, to the use of a large number of short trajectories. The short trajectories exploit a mapping to a mesh in coarse space and allow for efficient calculations of kinetics and thermodynamics. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081528DOI Listing

Gene Regulation in and out of Equilibrium.

Annu Rev Biophys 2020 May;49:199-226

Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

Determining whether and how a gene is transcribed are two of the central processes of life. The conceptual basis for understanding such gene regulation arose from pioneering biophysical studies in eubacteria. However, eukaryotic genomes exhibit vastly greater complexity, which raises questions not addressed by this bacterial paradigm. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081542DOI Listing

Light Microscopy of Mitochondria at the Nanoscale.

Annu Rev Biophys 2020 May 24;49:289-308. Epub 2020 Feb 24.

Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; email:

Mitochondria are essential for eukaryotic life. These double-membrane organelles often form highly dynamic tubular networks interacting with many cellular structures. Their highly convoluted contiguous inner membrane compartmentalizes the organelle, which is crucial for mitochondrial function. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081550DOI Listing

Insights into the Structure, Function, and Dynamics of the Bacterial Cytokinetic FtsZ-Ring.

Annu Rev Biophys 2020 May 24;49:309-341. Epub 2020 Feb 24.

Department of Biophysics & Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

The FtsZ protein is a highly conserved bacterial tubulin homolog. In vivo, the functional form of FtsZ is the polymeric, ring-like structure (Z-ring) assembled at the future division site during cell division. While it is clear that the Z-ring plays an essential role in orchestrating cytokinesis, precisely what its functions are and how these functions are achieved remain elusive. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081703DOI Listing

The Role of Conformational Dynamics and Allostery in Modulating Protein Evolution.

Annu Rev Biophys 2020 May 19;49:267-288. Epub 2020 Feb 19.

Center for Biological Physics, Department of Physics, Arizona State University, Tempe, Arizona 85281, USA; email:

Advances in sequencing techniques and statistical methods have made it possible not only to predict sequences of ancestral proteins but also to identify thousands of mutations in the human exome, some of which are disease associated. These developments have motivated numerous theories and raised many questions regarding the fundamental principles behind protein evolution, which have been traditionally investigated horizontally using the tip of the phylogenetic tree through comparative studies of extant proteins within a family. In this article, we review a vertical comparison of the modern and resurrected ancestral proteins. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115517DOI Listing
May 2020
15.436 Impact Factor

Predicting Evolution Using Regulatory Architecture.

Annu Rev Biophys 2020 May 4;49:181-197. Epub 2020 Feb 4.

Bionanoscience Department, Delft University of Technology, 2629HZ Delft, The Netherlands.

The limits of evolution have long fascinated biologists. However, the causes of evolutionary constraint have remained elusive due to a poor mechanistic understanding of studied phenotypes. Recently, a range of innovative approaches have leveraged mechanistic information on regulatory networks and cellular biology. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-032939DOI Listing

Temperature, Dynamics, and Enzyme-Catalyzed Reaction Rates.

Annu Rev Biophys 2020 May 4;49:163-180. Epub 2020 Feb 4.

Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom; email:

We review the adaptations of enzyme activity to different temperatures. Psychrophilic (cold-adapted) enzymes show significantly different activation parameters (lower activation enthalpies and entropies) from their mesophilic counterparts. Furthermore, there is increasing evidence that the temperature dependence of many enzyme-catalyzed reactions is more complex than is widely believed. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081520DOI Listing

RNA Droplets.

Annu Rev Biophys 2020 May 10;49:247-265. Epub 2020 Feb 10.

Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA; email:

Liquid-liquid phase separation is emerging as the universal mechanism by which membraneless cellular granules form. Despite many previous studies on condensation of intrinsically disordered proteins and low complexity domains, we lack understanding about the role of RNA, which is the essential component of all ribonucleoprotein (RNP) granules. RNA, as an anionic polymer, is inherently an excellent platform for achieving multivalency and can accommodate many RNA binding proteins. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115508DOI Listing

Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions.

Annu Rev Biophys 2020 May 31;49:107-133. Epub 2020 Jan 31.

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, 63130, USA; email:

Many biomolecular condensates appear to form via spontaneous or driven processes that have the hallmarks of intracellular phase transitions. This suggests that a common underlying physical framework might govern the formation of functionally and compositionally unrelated biomolecular condensates. In this review, we summarize recent work that leverages a stickers-and-spacers framework adapted from the field of associative polymers for understanding how multivalent protein and RNA molecules drive phase transitions that give rise to biomolecular condensates. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081629DOI Listing

Multifunctional Chaperone and Quality Control Complexes in Adaptive Immunity.

Annu Rev Biophys 2020 May 31;49:135-161. Epub 2020 Jan 31.

Institute of Biochemistry, Biocenter, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany; email:

The fundamental process of adaptive immunity relies on the differentiation of self from nonself. Nucleated cells are continuously monitored by effector cells of the immune system, which police the peptide status presented via cell surface molecules. Recent integrative structural approaches have provided insights toward our understanding of how sophisticated cellular machineries shape such hierarchical immune surveillance. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081643DOI Listing

Enhanced Diffusion and Chemotaxis of Enzymes.

Annu Rev Biophys 2020 May 27;49:87-105. Epub 2020 Jan 27.

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA; email:

Many enzymes appear to diffuse faster in the presence of substrate and to drift either up or down a concentration gradient of their substrate. Observations of these phenomena, termed enhanced enzyme diffusion (EED) and enzyme chemotaxis, respectively, lead to a novel view of enzymes as active matter. Enzyme chemotaxis and EED may be important in biology and could have practical applications in biotechnology and nanotechnology. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081535DOI Listing

Mitochondria-Associated Proteostasis.

Annu Rev Biophys 2020 May 13;49:41-67. Epub 2020 Jan 13.

Center for Cell Dynamics, Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Mitochondria are essential organelles in eukaryotes. Most mitochondrial proteins are encoded by the nuclear genome and translated in the cytosol. Nuclear-encoded mitochondrial proteins need to be imported, processed, folded, and assembled into their functional states. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081604DOI Listing

The Physics of Cellular Decision Making During Epithelial-Mesenchymal Transition.

Annu Rev Biophys 2020 May 8;49:1-18. Epub 2020 Jan 8.

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka 560012, India; email:

The epithelial-mesenchymal transition (EMT) is a process by which cells lose epithelial traits, such as cell-cell adhesion and apico-basal polarity, and acquire migratory and invasive traits. EMT is crucial to embryonic development and wound healing. Misregulated EMT has been implicated in processes associated with cancer aggressiveness, including metastasis. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081557DOI Listing

Principles and Applications of Biological Membrane Organization.

Annu Rev Biophys 2020 May 8;49:19-39. Epub 2020 Jan 8.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA; email:

Many critical biological events, including biochemical signaling, membrane traffic, and cell motility, originate at membrane surfaces. Each such event requires that members of a specific group of proteins and lipids rapidly assemble together at a specific site on the membrane surface. Understanding the biophysical mechanisms that stabilize these assemblies is critical to decoding and controlling cellular functions. Read More

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http://dx.doi.org/10.1146/annurev-biophys-121219-081637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299165PMC

Single-Molecule Studies on the Protein Translocon.

Annu Rev Biophys 2019 05;48:185-207

Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute; and the Zernike Institute for Advanced Materials, University of Groningen, 9747 AG Groningen, Netherlands; email:

Single-molecule studies provide unprecedented details about processes that are difficult to grasp by bulk biochemical assays that yield ensemble-averaged results. One of these processes is the translocation and insertion of proteins across and into the bacterial cytoplasmic membrane. This process is facilitated by the universally conserved secretion (Sec) system, a multi-subunit membrane protein complex that consists of dissociable cytoplasmic targeting components, a molecular motor, a protein-conducting membrane pore, and accessory membrane proteins. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115352DOI Listing
May 2019
2 Reads

Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene Expression.

Annu Rev Biophys 2019 05;48:121-163

Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.

It is tempting to believe that we now own the genome. The ability to read and rewrite it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles' heel exposed by all of the genomic data that has accrued: We still do not know how to interpret them. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001876PMC
May 2019
1 Read
15.436 Impact Factor

Programming Structured DNA Assemblies to Probe Biophysical Processes.

Annu Rev Biophys 2019 05;48:395-419

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:

Structural DNA nanotechnology is beginning to emerge as a widely accessible research tool to mechanistically study diverse biophysical processes. Enabled by scaffolded DNA origami in which a long single strand of DNA is weaved throughout an entire target nucleic acid assembly to ensure its proper folding, assemblies of nearly any geometric shape can now be programmed in a fully automatic manner to interface with biology on the 1-100-nm scale. Here, we review the major design and synthesis principles that have enabled the fabrication of a specific subclass of scaffolded DNA origami objects called wireframe assemblies. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035826PMC
May 2019
1 Read

RNA-Mediated Virus Assembly: Mechanisms and Consequences for Viral Evolution and Therapy.

Annu Rev Biophys 2019 05 5;48:495-514. Epub 2019 Apr 5.

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; email:

Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble at the nanoscale with exquisite precision-a key to their biological success in infection. Recent advances in structure determination and the development of biophysical tools such as single-molecule spectroscopy and noncovalent mass spectrometry allow unprecedented access to the detailed assembly mechanisms of simple virions. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biophys-05
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http://dx.doi.org/10.1146/annurev-biophys-052118-115611DOI Listing
May 2019
21 Reads

Regulation of Transmembrane Signaling by Phase Separation.

Annu Rev Biophys 2019 05 5;48:465-494. Epub 2019 Apr 5.

Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; email: , ,

Cell surface transmembrane receptors often form nanometer- to micrometer-scale clusters to initiate signal transduction in response to environmental cues. Extracellular ligand oligomerization, domain-domain interactions, and binding to multivalent proteins all contribute to cluster formation. Here we review the current understanding of mechanisms driving cluster formation in a series of representative receptor systems: glycosylated receptors, immune receptors, cell adhesion receptors, Wnt receptors, and receptor tyrosine kinases. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771929PMC
May 2019
1 Read

Structure and Assembly of the Nuclear Pore Complex.

Annu Rev Biophys 2019 05 3;48:515-536. Epub 2019 Apr 3.

Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany; email: , ,

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic exchange. They are exceptionally large protein complexes that fuse the inner and outer nuclear membranes to form channels across the nuclear envelope. About 30 different protein components, termed nucleoporins, assemble in multiple copies into an intricate cylindrical architecture. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115308DOI Listing
May 2019
4 Reads

Hybrid Live Cell-Supported Membrane Interfaces for Signaling Studies.

Annu Rev Biophys 2019 05 3;48:537-562. Epub 2019 Apr 3.

Department of Chemistry, University of California, Berkeley, California 94720, USA; email:

A wide range of cell-microenvironmental interactions are mediated by membrane-localized receptors that bind ligands present on another cell or the extracellular matrix. This situation introduces a number of physical effects including spatial organization of receptor-ligand complexes and development of mechanical forces in cells. Unlike traditional experimental approaches, hybrid live cell-supported lipid bilayer (SLB) systems, wherein a live cell interacts with a synthetic substrate supported membrane, allow interrogation of these aspects of receptor signaling. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033330DOI Listing
May 2019
13 Reads

Interrogating the Structural Dynamics and Energetics of Biomolecular Systems with Pressure Modulation.

Authors:
Roland Winter

Annu Rev Biophys 2019 05 3;48:441-463. Epub 2019 Apr 3.

Faculty of Chemistry and Chemical Biology, Biophysical Chemistry, TU Dortmund University, D-44227 Dortmund, Germany; email:

High hydrostatic pressure affects the structure, dynamics, and stability of biomolecular systems and is a key parameter in the context of the exploration of the origin and the physical limits of life. This review lays out the conceptual framework for exploring the conformational fluctuations, dynamical properties, and activity of biomolecular systems using pressure perturbation. Complementary pressure-jump relaxation studies are useful tools to study the kinetics and mechanisms of biomolecular phase transitions and structural transformations, such as membrane fusion or protein and nucleic acid folding. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115601DOI Listing
May 2019
1 Read

Understanding the Role of Lipids in Signaling Through Atomistic and Multiscale Simulations of Cell Membranes.

Annu Rev Biophys 2019 05;48:421-439

Computational Physics Laboratory, Tampere University, FI-33014 Tampere, Finland.

Cell signaling controls essentially all cellular processes. While it is often assumed that proteins are the key architects coordinating cell signaling, recent studies have shown more and more clearly that lipids are also involved in signaling processes in a number of ways. Lipids do, for instance, act as messengers, modulate membrane receptor conformation and dynamics, and control membrane receptor partitioning. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115553DOI Listing
May 2019
2 Reads

Polarizable Force Fields for Biomolecular Simulations: Recent Advances and Applications.

Annu Rev Biophys 2019 05 27;48:371-394. Epub 2019 Mar 27.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA; email:

Realistic modeling of biomolecular systems requires an accurate treatment of electrostatics, including electronic polarization. Due to recent advances in physical models, simulation algorithms, and computing hardware, biomolecular simulations with advanced force fields at biologically relevant timescales are becoming increasingly promising. These advancements have not only led to new biophysical insights but also afforded opportunities to advance our understanding of fundamental intermolecular forces. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520134PMC
May 2019
1 Read

An NMR View of Protein Dynamics in Health and Disease.

Annu Rev Biophys 2019 05 22;48:297-319. Epub 2019 Mar 22.

Departments of Molecular Genetics, Biochemistry, and Chemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada; email:

Biological molecules are often highly dynamic, and this flexibility can be critical for function. The large range of sampled timescales and the fact that many of the conformers that are continually explored are only transiently formed and sparsely populated challenge current biophysical approaches. Solution nuclear magnetic resonance (NMR) spectroscopy has emerged as a powerful method for characterizing biomolecular dynamics in detail, even in cases where excursions involve short-lived states. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115647DOI Listing
May 2019
2 Reads

Raman Imaging of Small Biomolecules.

Annu Rev Biophys 2019 05 20;48:347-369. Epub 2019 Mar 20.

Department of Chemistry, Columbia University, New York, NY 10027, USA; email:

Imaging techniques greatly facilitate the comprehensive knowledge of biological systems. Although imaging methodology for biomacromolecules such as protein and nucleic acids has been long established, microscopic techniques and contrast mechanisms are relatively limited for small biomolecules, which are equally important participants in biological processes. Recent developments in Raman imaging, including both microscopy and tailored vibrational tags, have created exciting opportunities for noninvasive imaging of small biomolecules in living cells, tissues, and organisms. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115500DOI Listing
May 2019
3 Reads

Biophysics of Chromatin Dynamics.

Annu Rev Biophys 2019 05 18;48:321-345. Epub 2019 Mar 18.

Department of Physics, Biophysics Graduate Program, Ohio State Biochemistry Graduate Program, and Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210-1117, USA; email:

Nucleosomes and chromatin control eukaryotic genome accessibility and thereby regulate DNA processes, including transcription, replication, and repair. Conformational dynamics within the nucleosome and chromatin structure play a key role in this regulatory function. Structural fluctuations continuously expose internal DNA sequences and nucleosome surfaces, thereby providing transient access for the nuclear machinery. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-032847DOI Listing
May 2019
7 Reads

Helicase Mechanisms During Homologous Recombination in .

Annu Rev Biophys 2019 05 11;48:255-273. Epub 2019 Mar 11.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; email: ,

Helicases are enzymes that move, manage, and manipulate nucleic acids. They can be subdivided into six super families and are required for all aspects of nucleic acid metabolism. In general, all helicases function by converting the chemical energy stored in the bond between the gamma and beta phosphates of adenosine triphosphate into mechanical work, which results in the unidirectional movement of the helicase protein along one strand of a nucleic acid. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642723PMC
May 2019
3 Reads

Generalized Born Implicit Solvent Models for Biomolecules.

Annu Rev Biophys 2019 05 11;48:275-296. Epub 2019 Mar 11.

Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA; email:

It would often be useful in computer simulations to use an implicit description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation and can be very efficient compared to the explicit treatment of the solvent. Here, we review a particular class of so-called fast implicit solvent models, generalized Born (GB) models, which are widely used for molecular dynamics (MD) simulations of proteins and nucleic acids. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biophys-05
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http://dx.doi.org/10.1146/annurev-biophys-052118-115325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645684PMC
May 2019
12 Reads

How the Genome Folds: The Biophysics of Four-Dimensional Chromatin Organization.

Annu Rev Biophys 2019 05 5;48:231-253. Epub 2019 Mar 5.

Unité Imagerie et Modélisation, CNRS UMR 3691, and C3BI (Center of Bioinformatics, Biostatistics and Integrative Biology), CNRS USR 3756, Institut Pasteur, 75015 Paris, France; email: , ,

The genetic information that instructs transcription and other cellular functions is carried by the chromosomes, polymers of DNA in complex with histones and other proteins. These polymers are folded inside nuclei five orders of magnitude smaller than their linear length, and many facets of this folding correlate with or are causally related to transcription and other cellular functions. Recent advances in sequencing and imaging-based techniques have enabled new views into several layers of chromatin organization. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115638DOI Listing
May 2019
3 Reads

Giant Vesicles and Their Use in Assays for Assessing Membrane Phase State, Curvature, Mechanics, and Electrical Properties.

Authors:
Rumiana Dimova

Annu Rev Biophys 2019 05 27;48:93-119. Epub 2019 Feb 27.

Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany; email:

Giant unilamellar vesicles represent a promising and extremely useful model biomembrane system for systematic measurements of mechanical, thermodynamic, electrical, and rheological properties of lipid bilayers as a function of membrane composition, surrounding media, and temperature. The most important advantage of giant vesicles over other model membrane systems is that the membrane responses to external factors such as ions, (macro)molecules, hydrodynamic flows, or electromagnetic fields can be directly observed under the microscope. Here, we briefly review approaches for giant vesicle preparation and describe several assays used for deducing the membrane phase state and measuring a number of material properties, with further emphasis on membrane reshaping and curvature. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115342DOI Listing
May 2019
1 Read

Mammalian Respiratory Complex I Through the Lens of Cryo-EM.

Annu Rev Biophys 2019 05 20;48:165-184. Epub 2019 Feb 20.

Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, United Kingdom; email: , , ,

Single-particle electron cryomicroscopy (cryo-EM) has led to a revolution in structural work on mammalian respiratory complex I. Complex I (mitochondrial NADH:ubiquinone oxidoreductase), a membrane-bound redox-driven proton pump, is one of the largest and most complicated enzymes in the mammalian cell. Rapid progress, following the first 5-Å resolution data on bovine complex I in 2014, has led to a model for mouse complex I at 3. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115704DOI Listing
May 2019
2 Reads

Membrane Electroporation and Electropermeabilization: Mechanisms and Models.

Annu Rev Biophys 2019 05 20;48:63-91. Epub 2019 Feb 20.

Faculty of Electrical Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia; email: ,

Exposure of biological cells to high-voltage, short-duration electric pulses causes a transient increase in their plasma membrane permeability, allowing transmembrane transport of otherwise impermeant molecules. In recent years, large steps were made in the understanding of underlying events. Formation of aqueous pores in the lipid bilayer is now a widely recognized mechanism, but evidence is growing that changes to individual membrane lipids and proteins also contribute, substantiating the need for terminological distinction between electroporation and electropermeabilization. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115451DOI Listing
May 2019
2 Reads

Split Green Fluorescent Proteins: Scope, Limitations, and Outlook.

Annu Rev Biophys 2019 05 20;48:19-44. Epub 2019 Feb 20.

Department of Chemistry, Stanford University, Stanford, California 94305, USA; email: ,

Many proteins can be split into fragments that spontaneously reassemble, without covalent linkage, into a functional protein. For split green fluorescent proteins (GFPs), fragment reassembly leads to a fluorescent readout, which has been widely used to investigate protein-protein interactions. We review the scope and limitations of this approach as well as other diverse applications of split GFPs as versatile sensors, molecular glues, optogenetic tools, and platforms for photophysical studies. Read More

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http://dx.doi.org/10.1146/annurev-biophys-051013-022846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537611PMC
May 2019
1 Read

How Good Can Single-Particle Cryo-EM Become? What Remains Before It Approaches Its Physical Limits?

Authors:
Robert M Glaeser

Annu Rev Biophys 2019 05 20;48:45-61. Epub 2019 Feb 20.

Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory and University of California, Berkeley, California 94720, USA; email:

Impressive though the achievements of single-particle cryo-electron microscopy are today, a substantial gap still remains between what is currently accomplished and what is theoretically possible. As is reviewed here, twofold or more improvements are possible as regards () the detective quantum efficiency of cameras at high resolution, () converting phase modulations to intensity modulations in the image, and () recovering the full amount of high-resolution signal in the presence of beam-induced motion of the specimen. In addition, potential for improvement is reviewed for other topics such as optimal choice of electron energy, use of aberration correctors, and quantum metrology. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-032828DOI Listing
May 2019
6 Reads

Mechanisms of Sensory Discrimination: Insights from Olfaction.

Annu Rev Biophys 2019 05 20;48:209-229. Epub 2019 Feb 20.

Centre for Neural Circuits and Behavior, University of Oxford, Oxford OX1 3SR, United Kingdom; email:

All an animal can do to infer the state of its environment is to observe the sensory-evoked activity of its own neurons. These inferences about the presence, quality, or similarity of objects are probabilistic and inform behavioral decisions that are often made in close to real time. Neural systems employ several strategies to facilitate sensory discrimination: Biophysical mechanisms separate the neuronal response distributions in coding space, compress their variances, and combine information from sequential observations. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115655DOI Listing
May 2019
2 Reads

Molecular Fitness Landscapes from High-Coverage Sequence Profiling.

Annu Rev Biophys 2019 05 2;48:1-18. Epub 2019 Jan 2.

Biomolecular Science and Engineering Program, University of California, Santa Barbara, California 93106, USA.

The function of fitness (or molecular activity) in the space of all possible sequences is known as the fitness landscape. Evolution is a random walk on the fitness landscape, with a bias toward climbing hills. Mapping the topography of real fitness landscapes is fundamental to understanding evolution, but previous efforts were hampered by the difficulty of obtaining large, quantitative data sets. Read More

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http://dx.doi.org/10.1146/annurev-biophys-052118-115333DOI Listing
May 2019
1 Read

Hydrogel-Tissue Chemistry: Principles and Applications.

Annu Rev Biophys 2018 05;47:355-376

Department of Bioengineering, Stanford University, Stanford, California 94305, USA; email:

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons-even within vertebrate brains. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-032905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359929PMC
May 2018
2 Reads

Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II.

Annu Rev Biophys 2018 05;47:425-446

Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; email:

RNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033058DOI Listing
May 2018
8 Reads

Substrate-Induced Formation of Ribosomal Decoding Center for Accurate and Rapid Genetic Code Translation.

Annu Rev Biophys 2018 05;47:525-548

Department of Cell and Molecular Biology, Uppsala University, Uppsala 75124, Sweden; email:

Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex ( T) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy ([Formula: see text]) of a particular protein synthesis system as its current accuracy and the effective selectivity ([Formula: see text]) as [Formula: see text] in the limit of zero ribosomal binding affinity for T. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biophys-06
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http://dx.doi.org/10.1146/annurev-biophys-060414-034148DOI Listing
May 2018
2 Reads

Macroscopic Theory for Evolving Biological Systems Akin to Thermodynamics.

Annu Rev Biophys 2018 05;47:273-290

Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan; email:

We present a macroscopic theory to characterize the plasticity, robustness, and evolvability of biological responses and their fluctuations. First, linear approximation in intracellular reaction dynamics is used to demonstrate proportional changes in the expression of all cellular components in response to a given environmental stress, with the proportion coefficient determined by the change in growth rate as a consequence of the steady growth of cells. We further demonstrate that this relationship is supported through adaptation experiments of bacteria, perhaps too well as this proportionality is held even across cultures of different types of conditions. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033155DOI Listing
May 2018
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The Physics of the Metaphase Spindle.

Annu Rev Biophys 2018 05;47:655-673

Max Planck Institute of Molecular Cell Biology and Genetics, 01307, Dresden, Germany; email:

The assembly of the mitotic spindle and the subsequent segregation of sister chromatids are based on the self-organized action of microtubule filaments, motor proteins, and other microtubule-associated proteins, which constitute the fundamental force-generating elements in the system. Many of the components in the spindle have been identified, but until recently it remained unclear how their collective behaviors resulted in such a robust bipolar structure. Here, we review the current understanding of the physics of the metaphase spindle that is only now starting to emerge. Read More

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http://dx.doi.org/10.1146/annurev-biophys-060414-034107DOI Listing
May 2018
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Molecular Mechanisms of Fast Neurotransmitter Release.

Annu Rev Biophys 2018 05;47:469-497

Department of Molecular and Cellular Physiology, Department of Neurology and Neurological Sciences, Department of Structural Biology, Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA; email:

This review summarizes current knowledge of synaptic proteins that are central to synaptic vesicle fusion in presynaptic active zones, including SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors), synaptotagmin, complexin, Munc18 (mammalian uncoordinated-18), and Munc13 (mammalian uncoordinated-13), and highlights recent insights in the cooperation of these proteins for neurotransmitter release. Structural and functional studies of the synaptic fusion machinery suggest new molecular models of synaptic vesicle priming and Ca-triggered fusion. These studies will be a stepping-stone toward answering the question of how the synaptic vesicle fusion machinery achieves such high speed and sensitivity. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070816-034117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378885PMC
May 2018
3 Reads

The Physical Properties of Ceramides in Membranes.

Annu Rev Biophys 2018 05 4;47:633-654. Epub 2018 Apr 4.

I nstituto Biofisika [University of the Basque Country and Spanish National Research Council (CSIC)], 48940 Leioa, Spain.

Ceramides are sphingolipids containing a sphingosine or a related base, to which a fatty acid is linked through an amide bond. When incorporated into a lipid bilayer, ceramides exhibit a number of properties not shared by almost any other membrane lipid: Ceramides ( a) are extremely hydrophobic and thus cannot exist in suspension in aqueous media; ( b) increase the molecular order (rigidity) of phospholipids in membranes; ( c) give rise to lateral phase separation and domain formation in phospholipid bilayers; ( d) possess a marked intrinsic negative curvature that facilitates formation of inverted hexagonal phases; ( e) make bilayers and cell membranes permeable to small and large (i.e. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033309DOI Listing
May 2018
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Behavioral Variability and Phenotypic Diversity in Bacterial Chemotaxis.

Annu Rev Biophys 2018 05 4;47:595-616. Epub 2018 Apr 4.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520; email:

Living cells detect and process external signals using signaling pathways that are affected by random fluctuations. These variations cause the behavior of individual cells to fluctuate over time (behavioral variability) and generate phenotypic differences between genetically identical individuals (phenotypic diversity). These two noise sources reduce our ability to predict biological behavior because they diversify cellular responses to identical signals. Read More

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http://dx.doi.org/10.1146/annurev-biophys-062215-010954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989721PMC
May 2018
3 Reads

Single-Molecule View of Small RNA-Guided Target Search and Recognition.

Annu Rev Biophys 2018 05 29;47:569-593. Epub 2018 Mar 29.

Kavli Institute of Nanoscience and Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, The Netherlands; email: , ,

Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-biophys-07
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http://dx.doi.org/10.1146/annurev-biophys-070317-032923DOI Listing
May 2018
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Structure and Immune Recognition of the HIV Glycan Shield.

Annu Rev Biophys 2018 May 29;47:499-523. Epub 2018 Mar 29.

Department of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California 92037, USA; email:

Vaccine design efforts against the human immunodeficiency virus (HIV) have been greatly stimulated by the observation that many infected patients eventually develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these bnAbs have evolved to recognize not only the two protein components of the viral envelope protein (Env) but also the numerous glycans that form a protective barrier on the Env protein. Because Env is heavily glycosylated compared to host glycoproteins, the glycans have become targets for the antibody response. Read More

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http://dx.doi.org/10.1146/annurev-biophys-060414-034156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163090PMC
May 2018
2 Reads

Dynamics of Bacterial Gene Regulatory Networks.

Annu Rev Biophys 2018 05 23;47:447-467. Epub 2018 Mar 23.

Department of Biosciences, Rice University, Houston, Texas 77005, USA; email:

The ability of bacterial cells to adjust their gene expression program in response to environmental perturbation is often critical for their survival. Recent experimental advances allowing us to quantitatively record gene expression dynamics in single cells and in populations coupled with mathematical modeling enable mechanistic understanding on how these responses are shaped by the underlying regulatory networks. Here, we review how the combination of local and global factors affect dynamical responses of gene regulatory networks. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-032947DOI Listing
May 2018
4 Reads

Dynamic Neutron Scattering by Biological Systems.

Annu Rev Biophys 2018 05 21;47:335-354. Epub 2018 Mar 21.

School of Physics and Astronomy and Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.

Dynamic neutron scattering directly probes motions in biological systems on femtosecond to microsecond timescales. When combined with molecular dynamics simulation and normal mode analysis, detailed descriptions of the forms and frequencies of motions can be derived. We examine vibrations in proteins, the temperature dependence of protein motions, and concepts describing the rich variety of motions detectable using neutrons in biological systems at physiological temperatures. Read More

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http://dx.doi.org/10.1146/annurev-biophys-070317-033358DOI Listing
May 2018
2 Reads