SwePub - sökning: L773:0959 440X OR L773:1879 03...

Numrering	Referens	Omslagsbild	Hitta
1.	Aqvist, Johan, et al. (författare) Bridging the gap between ribosome structure and biochemistry by mechanistic computations 2012 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 22:6, s. 815-823 Tidskriftsartikel (refereegranskat)abstract The wealth of structural and biochemical data now available for protein synthesis on the ribosome presents major new challenges for computational biochemistry. Apart from technical difficulties in modeling ribosome systems, the complexity of the overall translation cycle with a multitude of different kinetic steps presents a formidable problem for computational efforts where we have only seen the beginning. However, a range of methodologies including molecular dynamics simulations, free energy calculations, molecular docking and quantum chemical approaches have already been put to work with promising results. In particular, the combined efforts of structural biology, biochemistry, kinetics and computational modeling can lead towards a quantitative structure-based description of translation.
2.	Azinas, Stavros, et al. (författare) Cryo-EM uniqueness in structure determination of macromolecular complexes : A selected structural anthology 2023 Ingår i: Current opinion in structural biology. - 0959-440X .- 1879-033X. ; 81 Tidskriftsartikel (refereegranskat)abstract Cryogenic electron microscopy (cryo-EM) has become in the past 10 years one of the major tools for the structure determination of proteins. Nowadays, the structure prediction field is experiencing the same revolution and, using AlphaFold2, it is possible to have high-confidence atomic models for virtually any polypeptide chain, smaller than 4000 amino acids, in a simple click. Even in a scenario where all polypeptide chain folding were to be known, cryo-EM retains specific characteristics that make it a unique tool for the structure determination of macromolecular complexes. Using cryo-EM, it is possible to obtain near-atomic structures of large and flexible megacomplexes, describe conformational panoramas, and potentially develop a structural proteomic approach from fully ex vivo specimens.
3.	Bacic, Luka, et al. (författare) Recent advances in single-molecule fluorescence microscopy render structural biology dynamic 2020 Ingår i: Current opinion in structural biology. - LONDON ENGLAND : Elsevier BV. - 0959-440X .- 1879-033X. ; 65, s. 61-68 Tidskriftsartikel (refereegranskat)abstract Single-molecule fluorescence microscopy has long been appreciated as a powerful tool to study the structural dynamics that enable biological function of macromolecules. Recent years have witnessed the development of more complex single-molecule fluorescence techniques as well as powerful combinations with structural approaches to obtain mechanistic insights into the workings of various molecular machines and protein complexes. In this review, we highlight these developments that together bring us one step closer to a dynamic understanding of biological processes in atomic details.
4.	Ban, Nenad, et al. (författare) A new system for naming ribosomal proteins. 2014 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 24, s. 165-169 Tidskriftsartikel (refereegranskat)abstract A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names.
5.	Bryant, Patrick (författare) Deep learning for protein complex structure prediction 2023 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 79 Tidskriftsartikel (refereegranskat)abstract Recent developments in the structure prediction of protein complexes have resulted in accuracies rivalling experimental methods in many cases. The high accuracy is mainly observed in dimeric complexes and other problems such as protein disorder and predicting the structure of host-pathogen in-teractions remain. This review highlights the foundation for current accurate structure prediction of protein complexes and possible ways to address the remaining limitations.
6.	Carlsson, Jens, et al. (författare) Structure-based virtual screening of vast chemical space as a starting point for drug discovery 2024 Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 87 Tidskriftsartikel (refereegranskat)abstract Structure-based virtual screening aims to find molecules forming favorable interactions with a biological macromolecule using computational models of complexes. The recent surge of commercially available chemical space provides the opportunity to search for ligands of therapeutic targets among billions of compounds. This review offers a compact overview of structure-based virtual screens of vast chemical spaces, highlighting successful applications in early drug discovery for therapeutically important targets such as G protein-coupled receptors and viral enzymes. Emphasis is placed on strategies to explore ultra-large chemical libraries and synergies with emerging machine learning techniques. The current opportunities and future challenges of virtual screening are discussed, indicating that this approach will play an important role in the next-generation drug discovery pipeline.
7.	Carrasco Busturia, David, et al. (författare) Multiscale biomolecular simulations in the exascale era 2024 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 86 Tidskriftsartikel (refereegranskat)abstract The complexity of biological systems and processes, spanning molecular to macroscopic scales, necessitates the use of multiscale simulations to get a comprehensive understanding. lar dynamics (MD) simulations are crucial for capturing processes beyond the reach of classical MD simulations. The advent of exascale computing offers unprecedented opportunities for scientific exploration, not least within life sciences, where simulations are essential to unravel intricate molecular leveraging the immense computational power of exascale computing requires innovative algorithms and software designs. In this context, we discuss the current status and future prospects of multiscale biomolecular simulations on exascale supercomputers with a focus on QM/MM MD. We highlight our own efforts in developing a versatile and high-performance multiscale simulation framework with the aim of efficient utilization of state-of-the-art supercomputers. We showcase its application in uncovering complex biological mechanisms and its potential for leveraging exascale computing.
8.	Carreras-Puigvert, Jordi, et al. (författare) Artificial intelligence for high content imaging in drug discovery 2024 Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 87 Tidskriftsartikel (refereegranskat)abstract Artificial intelligence (AI) and high-content imaging (HCI) are contributing to advancements in drug discovery, propelled by the recent progress in deep neural networks. This review highlights AI's role in analysis of HCI data from fixed and livecell imaging, enabling novel label-free and multi-channel fluorescent screening methods, and improving compound profiling. HCI experiments are rapid and cost-effective, facilitating large data set accumulation for AI model training. However, the success of AI in drug discovery also depends on highquality data, reproducible experiments, and robust validation to ensure model performance. Despite challenges like the need for annotated compounds and managing vast image data, AI's potential in phenotypic screening and drug profiling is significant. Future improvements in AI, including increased interpretability and integration of multiple modalities, are expected to solidify AI and HCI's role in drug discovery.
9.	Choi, Seong Il, et al. (författare) A social distancing measure governing the whole proteome 2021 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 66, s. 104-111 Tidskriftsartikel (refereegranskat)abstract Protein folding in vivo has been largely understood in the context of molecular chaperones preventing aggregation of nascent polypeptides in the crowded cellular environment. Nascent chains utilize the crowded environment in favor of productive folding by direct physical connection with cellular macromolecules. The intermolecular repulsive forces by large excluded volume and surface charges of interacting cellular macromolecules, exerting ‘social distancing’ measure among folding intermediates, could play an important role in stabilizing their physically connected polypeptides against aggregation regardless of the physical connection types. The generic intrinsic chaperone activity of cellular macromolecules likely provides a robust cellular environment for the productive protein folding and solubility maintenance at the whole proteome level.
10.	Cortina, George A., et al. (författare) Predicting allostery and microbial drug resistance with molecular simulations 2018 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 52, s. 80-86 Tidskriftsartikel (refereegranskat)abstract Beta-lactamase enzymes mediate the most common forms of gram-negative antibiotic resistance affecting clinical treatment. They also constitute an excellent model system for the difficult problem of understanding how allosteric mutations can augment catalytic activity of already-competent enzymes. Multiple allosteric mutations have been identified that alter catalytic activity or drug-resistance spectrum in class A beta lactamases, but predicting these in advance continues to be challenging. Here, we review computational techniques based on structure and/or molecular simulation to predict such mutations. Structure-based techniques have been particularly helpful in developing graph algorithms for analyzing critical residues in beta-lactamase function, while classical molecular simulation has recently shown the ability to prospectively predict allosteric mutations increasing beta-lactamase activity and drug resistance. These will ultimately achieve the greatest power when combined with simulation methods that model reactive chemistry to calculate activation free energies directly.
11.	Daley, Daniel O (författare) The assembly of membrane proteins into complexes 2008 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 18:4, s. 420-4 Tidskriftsartikel (refereegranskat)abstract Protein complexes are a fundamental aspect of life in a membrane. It is therefore important to understand which proteins are assembled, and how the process of assembly is coordinated. To this end, a number of themes have emerged from the literature in recent years: first, membrane proteins assemble in an ordered, rather than a stochastic manner; second, they require chaperones to prevent unwanted interactions/aggregation; and third, they can be assembled into existing complexes. As these recurrent themes have emerged from studies on disparate complexes, they provide a general framework to understand the assembly of membrane proteins.
12.	Danielsson, Jens, et al. (författare) Comparing protein behaviour in vitro and in vivo, what does the data really tell us? 2017 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 42, s. 129-135 Tidskriftsartikel (refereegranskat)abstract The recent advancement in moving 'biophysical' analysis of proteins in vivo has finally brought us to a position where we can start to make quantitative comparisons with existing in-vitro data. A striking observation is that protein behaviour in live cells seems, after all, not that different from in test tubes, not even at the level of complex mechanisms like protein aggregation. The example examined in this review is the ALS associated protein SOD1 that apparently retains its in-vitro properties in vivo. Does this mean that the protocols for studying proteins in vivo are somehow oversimplified, or that the macromolecular properties and interplay despite being intrinsically malleable are evolutionary more 'streamlined' than previously anticipated? Whatever the answer may be the time is now right to put these data to critical biological test.
13.	Davey, Norman E., et al. (författare) The next wave of interactomics : Mapping the SLiM-based interactions of the intrinsically disordered proteome 2023 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 80 Tidskriftsartikel (refereegranskat)abstract Short linear motifs (SLiMs) are a unique and ubiquitous class of protein interaction modules that perform key regulatory functions and drive dynamic complex formation. For decades, interactions mediated by SLiMs have accumulated through detailed low-throughput experiments. Recent methodological advances have opened this previously underexplored area of the human interactome to high-throughput protein-protein interaction discovery. In this article, we discuss that SLiM-based interactions represent a significant blind spot in the current interactomics data, introduce the key methods that are illuminating the elusive SLiM-mediated interactome of the human cell on a large scale, and discuss the implications for the field.
14.	Elofsson, Arne, 1966- (författare) Progress at protein structure prediction, as seen in CASP15 2023 Ingår i: Current opinion in structural biology. - 0959-440X .- 1879-033X. ; 80 Forskningsöversikt (refereegranskat)abstract In Dec 2020, the results of AlphaFold version 2 were presented at CASP14, sparking a revolution in the field of protein structure predictions. For the first time, a purely computational method could challenge experimental accuracy for structure prediction of single protein domains. The code of AlphaFold v2 was released in the summer of 2021, and since then, it has been shown that it can be used to accurately predict the structure of most ordered proteins and many protein–protein interactions. It has also sparked an explosion of development in the field, improving AI-based methods to predict protein complexes, disordered regions, and protein design. Here I will review some of the inventions sparked by the release of AlphaFold.
15.	Gianni, Stefano, et al. (författare) Coupled binding and folding of intrinsically disordered proteins : what can we learn from kinetics? 2016 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 36, s. 18-24 Tidskriftsartikel (refereegranskat)abstract Protein or protein regions that are not forming well-defined structures in their free states under native-like conditions are called intrinsically disordered proteins. Such proteins are very common in protein-protein interactions, where their disorder apparently gives several advantages including optimal binding properties. To fully appreciate why protein disorder is advantageous for protein-protein interactions we need to understand the mechanism(s) of interaction. However, elucidating mechanisms in protein-protein interactions is usually very challenging. Here we discuss how kinetics in combination with protein engineering and structural information can be used to depict details of protein-protein interactions involving intrinsically disordered proteins.
16.	Gutsche, Irina, et al. (författare) Editorial overview: Biophysical methods: Multiple structures of proteins underpin their biological functions 2024 Ingår i: Current opinion in structural biology. - 0959-440X .- 1879-033X. ; 84 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
17.	Hebert, Hans (författare) CryoEM : a crystals to single particles round-trip 2019 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 58, s. 59-67 Tidskriftsartikel (refereegranskat)abstract In the era of intense and steadily increasing attention to cryo electron microscopy (cryoEM) as a powerful tool in structural biology, particularly with regard to randomly oriented biological macromolecules, studies of 2D and small 3D crystals using cryoEM provide added value for addressing-specific questions. Size and shape demands are not as restrictive as for single particle specimens. Crystallization may stabilize whole or partly flexible molecules. Resolutions beyond 2 A, for 3D crystals even sub-angstrom ngstrom structures, can be obtained allowing studies of chemical properties in detail. The electron dose can be kept low and reduce radiation damage for sensitive specimens. In contrast to X-ray crystallography, scattering of electrons will be directly related to the Coulomb potential and thus give information about charge distribution in biomolecules.
18.	Hebert, Hans, et al. (författare) The structure of membrane associated proteins in eicosanoid and glutathione metabolism as determined by electron crystallography 2007 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 17:4, s. 396-404 Forskningsöversikt (refereegranskat)abstract Membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) are involved in biosynthesis of arachidonic-derived mediators of pain, fever, and inflammation as well as in biotransformation and detoxification of electrophilic substances. Structure determination of microsomal glutathione transferase 1 using electron crystallography has provided the first atomic model of an MAPEG member. The homotrimer consists of three repeats of a four-helix transmembrane bundle with the largest extramembranous domain connecting the first and second helix and with a short proline rich loop on the same side between helices three and four. Residues of importance for intramolecular or intermolecular contacts as well as for stabilizing the active site have been identified and the results can be applied for interpreting structure-function relationship for similar MAPEG members.
19.	Hedfalk, Kristina, et al. (författare) Aquaporin gating 2006 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 16, s. 447-456 Forskningsöversikt (refereegranskat)abstract An acceleration in the rate at which new aquaporin structures are determined means that structural models are now available for mammalian AQP0, AQP1, AQP2 and AQP4, bacterial GlpF, AqpM and AQPZ, and the plant SoPIP2;1. With an apparent consensus emerging concerning the mechanism of selective water transport and proton extrusion, emphasis has shifted towards the issues of substrate selectivity and the mechanisms of aquaporin regulation. In particular, recently determined structures of plant SoPIP2;1, sheep and bovine AQP0, and Escherichia coli AQPZ provide new insights into the underlying structural mechanisms by which water transport rates are regulated in diverse organisms. From these results, two distinct pictures of 'capping' and 'pinching' have emerged to describe aquaporin gating.
20.	Hempel, Tim, et al. (författare) Markov field models: Scaling molecular kinetics approaches to large molecular machines 2022 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 77 Forskningsöversikt (refereegranskat)abstract With recent advances in structural biology, including experi-mental techniques and deep learning-enabled high-precision structure predictions, molecular dynamics methods that scale up to large biomolecular systems are required. Current state-of-the-art approaches in molecular dynamics modeling focus on encoding global configurations of molecular systems as distinct states. This paradigm commands us to map out all possible structures and sample transitions between them, a task that becomes impossible for large-scale systems such as biomolecular complexes. To arrive at scalable molecular models, we suggest moving away from global state de-scriptions to a set of coupled models that each describe the dynamics of local domains or sites of the molecular system. We describe limitations in the current state-of-the-art global -state Markovian modeling approaches and then introduce Markov field models as an umbrella term that includes models from various scientific communities, including Independent Markov decomposition, Ising and Potts models, and (dynamic) graphical models, and evaluate their use for computational molecular biology. Finally, we give a few examples of early adoptions of these ideas for modeling molecular kinetics and thermodynamics.
21.	Ivarsson, Ylva, et al. (författare) Affinity and specificity of motif-based protein-protein interactions 2019 Ingår i: Current opinion in structural biology. - : Current Biology. - 0959-440X .- 1879-033X. ; 54, s. 26-33 Forskningsöversikt (refereegranskat)abstract It is becoming increasingly clear that eukaryotic cell physiology is largely controlled by protein protein interactions involving disordered protein regions, which usually interact with globular domains in a coupled binding and folding reaction. Several protein recognition domains are part of large families where members can interact with similar peptide ligands. Because of this, much research has been devoted to understanding how specificity can be achieved. A combination of interface complementarity, interactions outside of the core binding site, avidity from multidomain architecture and spatial and temporal regulation of expression resolves the conundrum. Here, we review recent advances in molecular aspects of affinity and specificity in such protein-protein interactions.
22.	Ivarsson, Ylva, et al. (författare) Editorial overview : Folding and binding 2019 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 54, s. 139-140 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	Johansson, Linda C, 1983, et al. (författare) Membrane protein crystallization from lipidic phases 2009 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 19:4, s. 372-378 Tidskriftsartikel (refereegranskat)abstract Membrane protein structural biology is enjoying a steady acceleration in the rate of success. Nevertheless, numerous membrane protein targets are resistant to the traditional approach of directly crystallizing detergent solubilized and purified protein and the 'niche market' of lipidic phase crystallization is emerging as a powerful complement. These approaches, including lipidic cubic phase, lipidic sponge phase, and bicelle crystallization methods, all immerse purified membrane protein within a lipid rich matrix before crystallization. This environment is hypothesized to contribute to the protein's long-term structural stability and thereby favor crystallization. Spectacular recent successes include the high-resolution structures of the beta(2)-adrenergic G-protein-coupled receptor, the A(2A) adenosine G-protein-coupled receptor, and the mitochondrial voltage dependent anion channel. In combination with technical innovations aiming to popularize these methods, lipidic phase crystallization approaches can be expected to deliver an increasing scientific impact as the field develops.
24.	Kasson, Peter, et al. (författare) Adaptive ensemble simulations of biomolecules 2018 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 52, s. 87-94 Tidskriftsartikel (refereegranskat)abstract Recent advances in both theory and computational power have created opportunities to simulate biomolecular processes more efficiently using adaptive ensemble simulations. Ensemble simulations are now widely used to compute a number of individual simulation trajectories and analyze statistics across them. Adaptive ensemble simulations offer a further level of sophistication and flexibility by enabling high-level algorithms to control simulations-based on intermediate results. We review some of the adaptive ensemble algorithms and software infrastructure currently in use and outline where the complexities of implementing adaptive simulation have limited algorithmic innovation to date. We describe an adaptive ensemble API to overcome some of these barriers and more flexibly and simply express adaptive simulation algorithms to help realize the power of this type of simulation.
25.	Kjellén, Lena, et al. (författare) Specificity of glycosaminoglycan-protein interactions 2018 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 50, s. 101-108 Tidskriftsartikel (refereegranskat)abstract Glycosaminoglycans (GAGs) interact with a variety of proteins with important functions in development and homeostasis. Most of these proteins bind to heparin in vitro, a highly sulfated GAG species, although heparan sulfate and/or chondroitin/dermatan sulfate are more frequent physiological ligands. Binding affinity and specificity are determined by charge distribution, mainly due to sulfate and carboxylate groups and by GAG chain conformation. Interactions may be nonspecific, essentially reflecting charge density or highly specific, dependent on rare GAG-structural features. Yet other GAG epitopes bind protein ligands with intermediate specificity and variable affinity. Studies of heparan sulfate biosynthesis point to stochastic but strictly regulated, cell-specific polymer modification. Together, these features allow for graded modulation of protein functional response.
26.	Korolev, Nikolay, et al. (författare) Modelling chromatin structure and dynamics : status and prospects 2012 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 22:2, s. 151-159 Tidskriftsartikel (refereegranskat)abstract The packaging of genomic DNA into chromatin in the eukaryotic cell nucleus demands extensive compaction. This requires attractive nucleosome-nucleosome interactions to overcome repulsion between the negatively charged DNA segments as well as other constraints. At the same time, DNA must be dynamically accessible to the cellular machinery that operates on it. Recent progress in the experimental characterisation of the higher order structure and dynamics of well-defined chromatin fibres has stimulated the attempts at theoretical description of chromatin and the nucleosome. Here we review the present status of chromatin Modelling, with particular emphasis on coarse-grained computer simulation models, the role of electrostatic interactions, and discuss future perspectives in the field.
27.	Kreida, Stefan, et al. (författare) Structural insights into aquaporin selectivity and regulation. 2015 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 33, s. 126-134 Tidskriftsartikel (refereegranskat)abstract Aquaporins have emerged as one of the structurally best-characterized membrane protein families, with fourteen different structures available from a diverse range of organisms. While all aquaporins share the same fold and passive mechanism for water permeation, structural details allow for differences in selectivity and modes of regulation. These details are now the emphasis of aquaporin structural biology. Recent structural studies of eukaryotic aquaporins have revealed reoccurring structural themes in both gating and trafficking, implying a limited number of structural solutions to aquaporin regulation. Moreover, the groundbreaking subangstrom resolution structure of a yeast aquaporin allows hydrogens to be visualized in the water-conducting channel, providing exclusive new insights into the proton exclusion mechanism.
28.	Light, Sara, et al. (författare) Orphans and new gene origination, a structural and evolutionary perspective 2014 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 26, s. 73-83 Tidskriftsartikel (refereegranskat)abstract The frequency of de novo creation of proteins has been debated. Early it was assumed that de novo creation should be extremely rare and that the vast majority of all protein coding genes were created in early history of life. However, the early genomics era lead to the insight that protein coding genes do appear to be lineage-specific. Today, with thousands of completely sequenced genomes, this impression remains. It has even been proposed that the creation of novel genes, a continuous process where most de novo genes are short-lived, is as frequent as gene duplications. There exist reports with strongly indicative evidence for de novo gene emergence in many organisms ranging from Bacteria, sometimes generated through bacteriophages, to humans, where orphans appear to be overexpressed in brain and testis. In contrast, research on protein evolution indicates that many very distantly related proteins appear to share partial homology. Here, we discuss recent results on de novo gene emergence, as well as important technical challenges limiting our ability to get a definite answer to the extent of de novo protein creation.
29.	Light, Sara, et al. (författare) The impact of splicing on protein domain architecture 2013 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 23:3, s. 451-458 Tidskriftsartikel (refereegranskat)abstract Many proteins are composed of protein domains, functional units of common descent. Multidomain forms are common in all eukaryotes making up more than half of the proteome and the evolution of novel domain architecture has been accelerated in metazoans. It is also becoming increasingly clear that alternative splicing is prevalent among vertebrates. Given that protein domains are defined as structurally, functionally and evolutionarily distinct units, one may speculate that some alternative splicing events may lead to clean excisions of protein domains, thus generating a number of different domain architectures from one gene template. However, recent findings indicate that smaller alternative splicing events, in particular in disordered regions, might be more prominent than domain architectural changes.The problem of identifying protein isoforms is, however, still not resolved. Clearly, many splice forms identified through detection of mRNA sequences appear to produce 'nonfunctional' proteins, such as proteins with missing internal secondary structure elements. Here, we review the state of the art methods for identification of functional isoforms and present a summary of what is known, thus far, about alternative splicing with regard to protein domain architectures.
30.	Liljas, Anders, et al. (författare) Ribosomes - structure and function. 2012 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 22:6, s. 730-732 Forskningsöversikt (refereegranskat)
31.	Lindahl, Erik, 1972-, et al. (författare) Membrane proteins : molecular dynamics simulations 2008 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 18:4, s. 425-431 Tidskriftsartikel (refereegranskat)abstract Molecular dynamics simulations of membrane proteins are making rapid progress, because of new high-resolution structures, advances in computer hardware and atomistic simulation algorithms, and the recent introduction of coarse-grained models for membranes and proteins. In addition to several large ion channel simulations, recent studies have explored how individual amino acids interact with the bilayer or snorkel/anchor to the headgroup region, and it has been possible to calculate water/membrane partition free energies. This has resulted in a view of bilayers as being adaptive rather than purely hydrophobic solvents, with important implications, for example, for interaction between lipids and arginines in the charged S4 helix of voltage-gated ion channels. However, several studies indicate that the typical current simulations fall short of exhaustive sampling, and that even simple protein-membrane interactions require at least ca. 1 micros to fully sample their dynamics. One new way this is being addressed is coarse-grained models that enable mesoscopic simulations on multi-micros scale. These have been used to model interactions, self-assembly and membrane perturbations induced by proteins. While they cannot replace all-atom simulations, they are a potentially useful technique for initial insertion, placement, and low-resolution refinement.
32.	Marklund, Erik, Teknologie doktor, 1979-, et al. (författare) Weighing-up protein dynamics : the combination of native mass spectrometry and molecular dynamics simulations 2019 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 54, s. 50-58 Forskningsöversikt (refereegranskat)abstract Structural dynamics underpin biological function at the molecular level, yet many biophysical and structural biology approaches give only a static or averaged view of proteins. Native mass spectrometry yields spectra of the many states and interactions in the structural ensemble, but its spatial resolution is limited. Conversely, molecular dynamics simulations are innately high-resolution, but have a limited capacity for exploring all structural possibilities. The two techniques hence differ fundamentally in the information they provide, returning data that reflect different length scales and time scales, making them natural bedfellows. Here we discuss how the combination of native mass spectrometry with molecular dynamics simulations is enabling unprecedented insights into a range of biological questions by interrogating the motions of proteins, their assemblies, and interactions.
33.	Morgunova, E, et al. (författare) Structural insights into the interaction between transcription factors and the nucleosome 2021 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 71, s. 171-179 Tidskriftsartikel (refereegranskat)
34.	Morgunova, E, et al. (författare) Structural perspective of cooperative transcription factor binding 2017 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 47, s. 1-8 Tidskriftsartikel (refereegranskat)
35.	Neutze, Richard, 1969, et al. (författare) Membrane protein structural biology using X-ray free electron lasers 2015 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 33, s. 115-125 Tidskriftsartikel (refereegranskat)abstract © 2015 . Membrane protein structural biology has benefitted tremendously from access to micro-focus crystallography at synchrotron radiation sources. X-ray free electron lasers (XFELs) are linear accelerator driven X-ray sources that deliver a jump in peak X-ray brilliance of nine orders of magnitude and represent a disruptive technology with potential to dramatically change the field. Membrane proteins were amongst the first macromolecules to be studied with XFEL radiation and include proof-of-principle demonstrations of serial femtosecond crystallography (SFX), the observation that XFEL data can deliver damage free crystallographic structures, initial experiments towards recording structural information from 2D arrays of membrane proteins, and time-resolved SFX, time-resolved wide angle X-ray scattering and time-resolved X-ray emission spectroscopy studies. Conversely, serial crystallography methods are now being applied using synchrotron radiation. We believe that a context dependent choice of synchrotron or XFEL radiation will accelerate progress towards novel insights in understanding membrane protein structure and dynamics.
36.	Pabis, Anna, et al. (författare) Cooperativity and flexibility in enzyme evolution 2018 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 48, s. 83-92 Tidskriftsartikel (refereegranskat)abstract Enzymes are flexible catalysts, and there has been substantial discussion about the extent to which this flexibility contributes to their catalytic efficiency. What has been significantly less discussed is the extent to which this flexibility contributes to their evolvability. Despite this, recent years have seen an increasing number of both experimental and computational studies that demonstrate that cooperativity and flexibility play significant roles in enzyme innovation. This review covers key developments in the field that emphasize the importance of enzyme dynamics not just to the evolution of new enzyme function(s), but also as a property that can be harnessed in the design of new artificial enzymes.
37.	Pabis, Anna, et al. (författare) Promiscuity and electrostatic flexibility in the alkaline phosphatase superfamily 2016 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 37, s. 14-21 Tidskriftsartikel (refereegranskat)abstract Catalytic promiscuity, that is, the ability of single enzymes to facilitate the turnover of multiple, chemically distinct substrates, is a widespread phenomenon that plays an important role in the evolution of enzyme function. Additionally, such pre-existing multifunctionality can be harnessed in artificial enzyme design. The members of the alkaline phosphatase superfamily have served extensively as both experimental and computational model systems for enhancing our understanding of catalytic promiscuity. In this Opinion, we present key recent computational studies into the catalytic activity of these highly promiscuous enzymes, highlighting the valuable insight they have provided into both the molecular basis for catalytic promiscuity in general, and its implications for the evolution of phosphatase activity.
38.	Petrovic, Dusan, et al. (författare) Molecular modeling of conformational dynamics and its role in enzyme evolution 2018 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; , s. 50-57 Tidskriftsartikel (refereegranskat)abstract With increasing computational power, biomolecular simulations have become an invaluable tool for understanding enzyme mechanisms and the origins of enzyme catalysis. More recently, computational studies have started to focus on understanding how enzyme activity itself evolves, both in terms of enhancing the native or new activities on existing enzyme scaffolds, or completely de novo on previously non-catalytic scaffolds. In this context, both experiment and molecular modeling provided strong evidence for an important role of conformational dynamics in the evolution of enzyme functions. This contribution will present a brief overview of the current state of the art for computationally exploring enzyme conformational dynamics in enzyme evolution, and, using several showcase studies, illustrate the ways molecular modeling can be used to shed light on how enzyme function evolves, at the most fundamental molecular level.
39.	Shehu, Amarda, et al. (författare) Editorial overview : Theory and simulation and their new friends 2021 Ingår i: Current opinion in structural biology. - : CURRENT BIOLOGY LTD. - 0959-440X .- 1879-033X. ; 67, s. III-V Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
40.	Syrén, Per-Olof, et al. (författare) Squalene-hopene cyclases : evolution, dynamics and catalytic scope 2016 Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 41, s. 73-82 Tidskriftsartikel (refereegranskat)abstract Herein we highlight recent mechanistic findings on the impact of solvent dynamics on catalysis displayed by squalene-hopene cyclases (SHCs). These fascinating biocatalysts that appeared early during the evolution of terpene biosynthetic machineries exploit a catalytic aspartic acid donating the anti-oriented proton to the terminal C. C double bond of pre-folded isoprenoid substrates. We review how the unusual strength of this Brønsted acid can be used to harness a plethora of non-natural protonation-driven reactions in a plastic enzyme fold. Moreover, recent results underline how the reaction termination by deprotonation or water addition is governed by the spatial location of water in the active site. Site-directed mutagenesis of amino acids located in the hydrophobic binding pocket allows for the generation of novel catalytic function by active site reshaping with relatively small enzyme libraries. A deepened understanding of triterpene cyclase dynamics in concert with chemical expertise thus have a great potential to allow for the biocatalytic manufacturing of tailored building bricks that would expand the chemical repertoire currently found in nature.
41.	Söderholm, Niklas, et al. (författare) Exploring the bacterial nano-universe 2020 Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 64, s. 166-173 Forskningsöversikt (refereegranskat)abstract Since the days of the first acknowledged microscopist, Antonie van Leeuwenhoek, the 'animalcules', that is, bacteria and other microbes have been subject to increasingly detailed visualization. With the currently most sophisticated molecular imaging method; cryo electron tomography (Cryo-ET), we are reaching the milestone of being able to image an entire organism in a single dataset at nanometer resolution. Cryo-ET will enable the next revolution in our understanding of bacterial cells, their ultra-structure and intricate molecular nanomachines. Here, we highlight recent research discoveries based on constantly progressing technology developments. We discuss advantages and challenges of using Cryo-ET to visualize spatial structure of microorganisms and macromolecular complexes in their native environment.
42.	Travaglini-Allocatelli, Carlo, et al. (författare) Folding and stability of globular proteins and implications for function 2009 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 19:1, s. 3-7 Tidskriftsartikel (refereegranskat)abstract The description of protein folding pathways and the principles that govern them has proven to be one of the most difficult problems to be solved in structural biology. But the combination of experiments and simulations has now provided a clearer picture of the chemistry involved. Once folded, however, proteins remain dynamic systems making possible both small-scale and large-scale structural and/or dynamical changes upon binding or releasing of ligands and during catalysis. In this review we focus on recent advances in the field of protein folding and discuss possible links between folding, stability, and binding dynamics.
43.	Tsirigos, Konstantinos D., et al. (författare) Topology of membrane proteins - predictions, limitations and variations 2018 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 50, s. 9-17 Tidskriftsartikel (refereegranskat)abstract Transmembrane proteins perform a variety of important biological functions necessary for the survival and growth of the cells. Membrane proteins are built up by transmembrane segments that span the lipid bilayer. The segments can either be in the form of hydrophobic alpha-helices or beta-sheets which create a barrel. A fundamental aspect of the structure of transmembrane proteins is the membrane topology, that is, the number of transmembrane segments, their position in the protein sequence and their orientation in the membrane. Along these lines, many predictive algorithms for the prediction of the topology of alpha-helical and beta-barrel transmembrane proteins exist. The newest algorithms obtain an accuracy close to 80% both for alpha-helical and beta-barrel transmembrane proteins. However, lately it has been shown that the simplified picture presented when describing a protein family by its topology is limited. To demonstrate this, we highlight examples where the topology is either not conserved in a protein superfamily or where the structure cannot be described solely by the topology of a protein. The prediction of these nonstandard features from sequence alone was not successful until the recent revolutionary progress in 3D-structure prediction of proteins.
44.	Vallina Estrada, Eloy, 1993-, et al. (författare) Diffusive intracellular interactions : On the role of protein net charge and functional adaptation 2023 Ingår i: Current Opinion in Structural Biology. - 0959-440X .- 1879-033X. ; 81 Forskningsöversikt (refereegranskat)abstract A striking feature of nucleic acids and lipid membranes is that they all carry net negative charge and so is true for the majority of intracellular proteins. It is suggested that the role of this negative charge is to assure a basal intermolecular repulsion that keeps the cytosolic content suitably ‘fluid’ for function. We focus in this review on the experimental, theoretical and genetic findings which serve to underpin this idea and the new questions they raise. Unlike the situation in test tubes, any functional protein-protein interaction in the cytosol is subject to competition from the densely crowded background, i.e. surrounding stickiness. At the nonspecific limit of this stickiness is the ‘random’ protein-protein association, maintaining profuse populations of transient and constantly interconverting complexes at physiological protein concentrations. The phenomenon is readily quantified in studies of the protein rotational diffusion, showing that the more net negatively charged a protein is the less it is retarded by clustering. It is further evident that this dynamic protein-protein interplay is under evolutionary control and finely tuned across organisms to maintain optimal physicochemical conditions for the cellular processes. The emerging picture is then that specific cellular function relies on close competition between numerous weak and strong interactions, and where all parts of the protein surfaces are involved. The outstanding challenge is now to decipher the very basics of this many-body system: how the detailed patterns of charged, polar and hydrophobic side chains not only control protein-protein interactions at close- and long-range but also the collective properties of the cellular interior as a whole.
45.	Van der Spoel, David (författare) Systematic design of biomolecular force fields 2021 Ingår i: Current opinion in structural biology. - : Elsevier. - 0959-440X .- 1879-033X. ; 67, s. 18-24 Forskningsöversikt (refereegranskat)abstract Force fields for the study of biomolecules have been developed in a predominantly organic manner by regular updates over half a century. Together with better algorithms and advances in computer technology, force fields have improved to yield more robust predictions. However, there are also indications to suggest that intramolecular energy functions have not become better and that there still is room for improvement. In this review, systematic efforts toward development of novel force fields from scratch are described. This includes an estimate of the complexity of the problem and the prerequisites in the form of data and algorithms. It is suggested that in order to make progress, an effort is needed to standardize reference data and force field validation benchmarks.
46.	Westenhoff, Sebastian, 1978, et al. (författare) Protein motions visualized by femtosecond time-resolved crystallography: The case of photosensory vs photosynthetic proteins 2022 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 77 Tidskriftsartikel (refereegranskat)abstract Proteins are dynamic objects and undergo conformational changes when functioning. These changes range from inter -conversion between states in equilibrium to ultrafast and coherent structural motions within one perturbed state. Time -resolved serial femtosecond crystallography at free-electron X-ray lasers can unravel structural changes with atomic reso-lution and down to femtosecond time scales. In this review, we summarize recent advances on detecting structural changes for phytochrome photosensor proteins and a bacterial photosyn-thetic reaction center. In the phytochrome structural changes are extensive and involve major rearrangements of many amino acids and water molecules, accompanying the regulation of its biochemical activity, whereas in the photosynthetic reaction center protein the structural changes are smaller, more local-ized, and are optimized to facilitate electron transfer along the chromophores. The detected structural motions underpin the proteins' function, providing a showcase for the importance of detecting ultrafast protein structural dynamics.
47.	Wittung Stafshede, Pernilla, 1968 (författare) Gut power: Modulation of human amyloid formation by amyloidogenic proteins in the gastrointestinal tract 2022 Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 72, s. 33-38 Forskningsöversikt (refereegranskat)abstract Protein assembly into amyloid fibers underlies many neurodegenerative disorders. In Parkinson's disease, amyloid formation of α-synuclein is linked to brain cell death. The gut–brain axis plays a key role in Parkinson's disease, and initial α-synuclein amyloid formation may occur distant from the brain. Because different amyloidogenic proteins can cross-seed, and α-synuclein is expressed outside the brain, amyloids present in the gut (from food products and secreted by microbiota) may modulate α-synuclein amyloid formation via direct interactions. I here describe existing such data that only began to appear in the literature in the last few years. The striking, but limited, data set—spanning from acceleration to inhibition—calls for additional investigations that may unravel disease mechanisms as well as new treatments.
48.	Wright, SC, et al. (författare) Illuminating the complexity of GPCR pathway selectivity - advances in biosensor development 2021 Ingår i: Current opinion in structural biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 69, s. 142-149 Tidskriftsartikel (refereegranskat)
49.	Branden, CI, et al. (författare) Proteins 1997 Ingår i: Current opinion in structural biology. - 0959-440X. ; 7:6, s. 819-820 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
50.	Lindqvist, Y, et al. (författare) Circular permutations of natural protein sequences: structural evidence 1997 Ingår i: Current opinion in structural biology. - 0959-440X. ; 7:3, s. 422-427 Tidskriftsartikel (refereegranskat)

Skapa referenser, mejla, bekava och länka

Länka till träfflistan

Träfflista för sökning "L773:0959 440X OR L773:1879 033X "

Avgränsa träffmängd

År