Structural Dynamics-Us最新文献

{"title":"Deep mining of the protein energy landscape.","authors":"A Joshua Wand","doi":"10.1063/4.0000180","DOIUrl":"https://doi.org/10.1063/4.0000180","url":null,"abstract":"<p><p>For over half a century, it has been known that protein molecules naturally undergo extensive structural fluctuations, and that these internal motions are intimately related to their functional properties. The energy landscape view has provided a powerful framework for describing the various physical states that proteins visit during their lifetimes. This Perspective focuses on the commonly neglected and often disparaged axis of the protein energy landscape: entropy. Initially seen largely as a barrier to functionally relevant states of protein molecules, it has recently become clear that proteins retain considerable conformational entropy in the \"native\" state, and that this entropy can and often does contribute significantly to the free energy of fundamental protein properties, processes, and functions. NMR spectroscopy, molecular dynamics simulations, and emerging crystallographic views have matured in parallel to illuminate dynamic disorder of the \"ground state\" of proteins and their importance in not only transiting between biologically interesting structures but also greatly influencing their stability, cooperativity, and contribution to critical properties such as allostery.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular size dependence on achievable resolution from XFEL single-particle 3D reconstruction.","authors":"Miki Nakano,&nbsp;Osamu Miyashita,&nbsp;Florence Tama","doi":"10.1063/4.0000175","DOIUrl":"https://doi.org/10.1063/4.0000175","url":null,"abstract":"<p><p>Single-particle analysis using x-ray free-electron lasers (XFELs) is a novel method for obtaining structural information of samples in a state close to nature. In particular, it is suitable for observing the inner structure of large biomolecules by taking advantage of the high transmittance of x-rays. However, systematic studies on the resolution achievable for large molecules are lacking. In this study, the molecular size dependence of the resolution of a three-dimensional (3D) structure resulting from XFEL single-particle reconstruction is evaluated using synthetic data. Evidently, 3D structures of larger molecules can be restored with higher detail (defined relative to the molecular sizes) than smaller ones; however, reconstruction with high absolute resolution (defined in nm^-1) is challenging. Our results provide useful information for the experimental design of 3D structure reconstruction using coherent x-ray diffraction patterns of single-particles.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein dynamics: The future is bright and complicated!","authors":"Kwangho Nam, Magnus Wolf-Watz","doi":"10.1063/4.0000179","DOIUrl":"10.1063/4.0000179","url":null,"abstract":"<p><p>Biological life depends on motion, and this manifests itself in proteins that display motion over a formidable range of time scales spanning from femtoseconds vibrations of atoms at enzymatic transition states, all the way to slow domain motions occurring on micro to milliseconds. An outstanding challenge in contemporary biophysics and structural biology is a quantitative understanding of the linkages among protein structure, dynamics, and function. These linkages are becoming increasingly explorable due to conceptual and methodological advances. In this Perspective article, we will point toward future directions of the field of protein dynamics with an emphasis on enzymes. Research questions in the field are becoming increasingly complex such as the mechanistic understanding of high-order interaction networks in allosteric signal propagation through a protein matrix, or the connection between local and collective motions. In analogy to the solution to the \"protein folding problem,\" we argue that the way forward to understanding these and other important questions lies in the successful integration of experiment and computation, while utilizing the present rapid expansion of sequence and structure space. Looking forward, the future is bright, and we are in a period where we are on the doorstep to, at least in part, comprehend the importance of dynamics for biological function.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological function investigated by time-resolved structure determination.","authors":"Marius Schmidt","doi":"10.1063/4.0000177","DOIUrl":"10.1063/4.0000177","url":null,"abstract":"<p><p>Inspired by recent progress in time-resolved x-ray crystallography and the adoption of time-resolution by cryo-electronmicroscopy, this article enumerates several approaches developed to become bigger/smaller, faster, and better to gain new insight into the molecular mechanisms of life. This is illustrated by examples where chemical and physical stimuli spawn biological responses on various length and time-scales, from fractions of Ångströms to micro-meters and from femtoseconds to hours.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10782838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of trioleoylglycerol two-layer and adiposome cross-section mimicking four-layer systems through atomic-level simulations.","authors":"Ahmed Hammad Mirza","doi":"10.1063/4.0000168","DOIUrl":"10.1063/4.0000168","url":null,"abstract":"<p><p>Adiposomes are artificially prepared lipid droplet (LD)-mimetic structures, which, unlike LDs, do not harbor proteins. The dynamics of interaction between triacylglycerols (TAGs), drug molecule, and phospholipids in adiposomes is currently not well-established. Trioleoylglycerol (TOG) molecule was divided into three parts: two oleoyl tails and one 2-monooleoylglycerol (MOG). Forcefield parameters for two oleoyl tails were adopted from the AMBER18 repository while that of the MOG forcefield was taken from the literature. Charge correction was performed on the MOG forcefield before its utilization. After charge correction, the resulting TOG molecule had zero charge. TOG bilayer (2L) and tetralayer (4L) systems were prepared and simulated. TOG bilayer (2L) systems-modeled from two different initial conformations, the TOG3 conformation and the TOG2:1 conformation-showed that TOG2:1 conformation was more prevailing irrespective of the starting conformation and was subsequently used in further simulations. The hydrated TOG 2L system showed TOG-water solution solubility of 0.051 mol L^-1 which is near experimental values. This validated the correct parameterization of the TOG molecule. The simulations of 4L systems showed stable membrane behaviors toward the end of simulations. It was also observed that in the 4L system, the TOG molecules showed the formation of micelles with the drug molecule. Almost six TOGs remained continuously in contact with the drug molecule throughout the simulation. The availability of charge-corrected TOG parameterization is expected to equip future studies with a framework for molecular dynamics simulations of adiposomes and/or LDs at the atomic level.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expected resolution limits of x-ray free-electron laser single-particle imaging for realistic source and detector properties.","authors":"Juncheng E,&nbsp;Y Kim,&nbsp;J Bielecki,&nbsp;M Sikorski,&nbsp;R de Wijn,&nbsp;C Fortmann-Grote,&nbsp;J Sztuk-Dambietz,&nbsp;J C P Koliyadu,&nbsp;R Letrun,&nbsp;H J Kirkwood,&nbsp;T Sato,&nbsp;R Bean,&nbsp;A P Mancuso,&nbsp;C Kim","doi":"10.1063/4.0000169","DOIUrl":"https://doi.org/10.1063/4.0000169","url":null,"abstract":"<p><p>The unprecedented intensity of x-ray free-electron laser sources has enabled single-particle x-ray diffraction imaging (SPI) of various biological specimens in both two-dimensional projection and three dimensions (3D). The potential of studying protein dynamics in their native conditions, without crystallization or chemical staining, has encouraged researchers to aim for increasingly higher resolutions with this technique. The currently achievable resolution of SPI is limited to the sub-10 nanometer range, mainly due to background effects, such as instrumental noise and parasitic scattering from the carrier gas used for sample delivery. Recent theoretical studies have quantified the effects of x-ray pulse parameters, as well as the required number of diffraction patterns to achieve a certain resolution, in a 3D reconstruction, although the effects of detector noise and the random particle orientation in each diffraction snapshot were not taken into account. In this work, we show these shortcomings and address limitations on achievable image resolution imposed by the adaptive gain integrating pixel detector noise.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40480826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charge-induced chemical dynamics in glycine probed with time-resolved Auger electron spectroscopy.","authors":"David Schwickert,&nbsp;Marco Ruberti,&nbsp;Přemysl Kolorenč,&nbsp;Andreas Przystawik,&nbsp;Slawomir Skruszewicz,&nbsp;Malte Sumfleth,&nbsp;Markus Braune,&nbsp;Lars Bocklage,&nbsp;Luis Carretero,&nbsp;Marie Kristin Czwalinna,&nbsp;Dian Diaman,&nbsp;Stefan Düsterer,&nbsp;Marion Kuhlmann,&nbsp;Steffen Palutke,&nbsp;Ralf Röhlsberger,&nbsp;Juliane Rönsch-Schulenburg,&nbsp;Sven Toleikis,&nbsp;Sergey Usenko,&nbsp;Jens Viefhaus,&nbsp;Anton Vorobiov,&nbsp;Michael Martins,&nbsp;Detlef Kip,&nbsp;Vitali Averbukh,&nbsp;Jon P Marangos,&nbsp;Tim Laarmann","doi":"10.1063/4.0000165","DOIUrl":"https://doi.org/10.1063/4.0000165","url":null,"abstract":"<p><p>In the present contribution, we use x-rays to monitor charge-induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x-ray pulses track the induced coherence through resonant x-ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time-resolved x-ray absorption measurement, we monitor the time-frequency spectra of the resulting many-body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump-probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of <math><mrow><mo>(</mo> <mo>-</mo> <mn>0.3</mn> <mo>±</mo> <mn>0.1</mn> <mo>)</mo> <mi>π</mi> <mo>≤</mo> <mi>ϕ</mi> <mo>≤</mo> <mo>(</mo> <mn>0.1</mn> <mo>±</mo> <mn>0.2</mn> <mo>)</mo> <mi>π</mi></mrow> </math> and <math> <mrow> <msubsup><mrow><mn>18.2</mn></mrow> <mrow><mo>-</mo> <mn>1.4</mn></mrow> <mrow><mo>+</mo> <mn>1.7</mn></mrow> </msubsup> <mo>≤</mo> <mi>T</mi> <mo>≤</mo> <msubsup><mrow><mn>23.9</mn></mrow> <mrow><mo>-</mo> <mn>1.1</mn></mrow> <mrow><mo>+</mo> <mn>1.2</mn></mrow> </msubsup> </mrow> </math> fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge-induced bond cleavage along different reaction coordinates.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40481439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solution characterization of the dynamic conjugative entry exclusion protein TraG.","authors":"Nicholas Bragagnolo,&nbsp;Gerald F Audette","doi":"10.1063/4.0000171","DOIUrl":"https://doi.org/10.1063/4.0000171","url":null,"abstract":"<p><p>The R100 plasmid and the secretion system it encodes are representative of F-like conjugative type IV secretion systems for the transmission of mobile DNA elements in gram-negative bacteria, serving as a major contributor to the spread of antibiotic resistance in bacterial pathogens. The TraG protein of F-like systems consists of a membrane-bound N-terminal domain and a periplasmic C-terminal domain, denoted TraG*. TraG* is essential in preventing redundant DNA transfer through a process termed entry exclusion. In the donor cell, it interacts with TraN to facilitate mating pair stabilization; however, if a mating pore forms between bacteria with identical plasmids, TraG* interacts with its cognate TraS in the inner membrane of the recipient bacterium to prevent redundant donor-donor conjugation. Structural studies of TraG* from the R100 plasmid have revealed the presence of a dynamic region between the N- and C-terminal domains of TraG. Thermofluor, circular dichroism, collision-induced unfolding-mass spectrometry, and size exclusion chromatography linked to multiangle light scattering and small angle x-ray scattering experiments indicated an N-terminal truncation mutant displayed higher stability and less disordered content relative to full-length TraG*. The 45 N-terminal residues of TraG* are hypothesized to serve as part of a flexible linker between the two independently functioning domains.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10465923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate quantification of lattice temperature dynamics from ultrafast electron diffraction of single-crystal films using dynamical scattering simulations.","authors":"Daniel B Durham,&nbsp;Colin Ophus,&nbsp;Khalid M Siddiqui,&nbsp;Andrew M Minor,&nbsp;Daniele Filippetto","doi":"10.1063/4.0000170","DOIUrl":"https://doi.org/10.1063/4.0000170","url":null,"abstract":"<p><p>In ultrafast electron diffraction (UED) experiments, accurate retrieval of time-resolved structural parameters, such as atomic coordinates and thermal displacement parameters, requires an accurate scattering model. Unfortunately, kinematical models are often inaccurate even for relativistic electron probes, especially for dense, oriented single crystals where strong channeling and multiple scattering effects are present. This article introduces and demonstrates dynamical scattering models tailored for quantitative analysis of UED experiments performed on single-crystal films. As a case study, we examine ultrafast laser heating of single-crystal gold films. Comparison of kinematical and dynamical models reveals the strong effects of dynamical scattering within nm-scale films and their dependence on sample topography and probe kinetic energy. Applying to UED experiments on an 11 nm thick film using 750 keV electron probe pulses, the dynamical models provide a tenfold improvement over a comparable kinematical model in matching the measured UED patterns. Also, the retrieved lattice temperature rise is in very good agreement with predictions based on previously measured optical constants of gold, whereas fitting the Debye-Waller factor retrieves values that are more than three times lower. Altogether, these results show the importance of a dynamical scattering theory for quantitative analysis of UED and demonstrate models that can be practically applied to single-crystal materials and heterostructures.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9726223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling difference x-ray scattering observations from an integral membrane protein within a detergent micelle.","authors":"Daniel Sarabi, Lucija Ostojić, Robert Bosman, Adams Vallejos, Johanna-Barbara Linse, Michael Wulff, Matteo Levantino, Richard Neutze","doi":"10.1063/4.0000157","DOIUrl":"10.1063/4.0000157","url":null,"abstract":"<p><p>Time-resolved x-ray solution scattering (TR-XSS) is a sub-field of structural biology, which observes secondary structural changes in proteins as they evolve along their functional pathways. While the number of distinct conformational states and their rise and decay can be extracted directly from TR-XSS experimental data recorded from light-sensitive systems, structural modeling is more challenging. This step often builds from complementary structural information, including secondary structural changes extracted from crystallographic studies or molecular dynamics simulations. When working with integral membrane proteins, another challenge arises because x-ray scattering from the protein and the surrounding detergent micelle interfere and these effects should be considered during structural modeling. Here, we utilize molecular dynamics simulations to explicitly incorporate the x-ray scattering cross term between a membrane protein and its surrounding detergent micelle when modeling TR-XSS data from photoactivated samples of detergent solubilized bacteriorhodopsin. This analysis provides theoretical foundations in support of our earlier approach to structural modeling that did not explicitly incorporate this cross term and improves agreement between experimental data and theoretical predictions at lower x-ray scattering angles.</p>","PeriodicalId":48683,"journal":{"name":"Structural Dynamics-Us","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40465526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}