Author
Dmitri I. Svergun
Other affiliations: University of Massachusetts Medical School, University of Hamburg, Adam Mickiewicz University in Poznań ...read more
Bio: Dmitri I. Svergun is an academic researcher from European Bioinformatics Institute. The author has contributed to research in topics: Small-angle X-ray scattering & Protein structure. The author has an hindex of 83, co-authored 576 publications receiving 48619 citations. Previous affiliations of Dmitri I. Svergun include University of Massachusetts Medical School & University of Hamburg.
Papers published on a yearly basis
Papers
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TL;DR: The average ensemble structure of the intrinsically disordered N-terminal transactivation domain (TAD) is determined by using residual dipolar couplings from NMR spectroscopy and small-angle x-ray scattering (SAXS) to model the disordered termini and the folded domains in the complex with DNA.
Abstract: Proteins with intrinsically disordered domains are implicated in a vast range of biological processes, especially in cell signaling and regulation. Having solved the quaternary structure of the folded domains in the tumor suppressor p53 by a multidisciplinary approach, we have now determined the average ensemble structure of the intrinsically disordered N-terminal transactivation domain (TAD) by using residual dipolar couplings (RDCs) from NMR spectroscopy and small-angle x-ray scattering (SAXS). Remarkably, not only were we able to measure RDCs of the isolated TAD, but we were also able to do so for the TAD in both the full-length tetrameric p53 protein and in its complex with a specific DNA response element. We determined the orientation of the TAD ensemble relative to the core domain, found that the TAD was stiffer in the proline-rich region (residues 64–92), which has a tendency to adopt a polyproline II (PPII) structure, and projected the TAD away from the core. We located the TAD in SAXS experiments on a complex between tetrameric p53 and four Taz2 domains that bind tightly to the TAD (residues 1–57) and acted as “reporters.” The p53-Taz2 complex was an extended cross-shaped structure. The quality of the SAXS data enabled us to model the disordered termini and the folded domains in the complex with DNA. The core domains enveloped the response element in the center of the molecule, with the Taz2-bound TADs projecting outward from the core.
380 citations
TL;DR: In this article, the molecular mass (MM) of a monodisperse protein solution is calculated from the extrapolated scattering intensity at zero angle I(0), which provides valuable information about the oligomeric state and absence of unspecific aggregation.
Abstract: One of the most important overall parameters, which can be derived from small-angle X-ray scattering (SAXS) experiments on macromolecular solutions is the molecular mass (MM) of the solute. In particular, for a monodisperse protein solution, MM of the solute is calculated from the extrapolated scattering intensity at zero angle I(0). Assessing MM by SAXS provides valuable information about the oligomeric state and absence of unspecific aggregation in solution. The value of MM can either be estimated by comparison with a protein standard with a known MM or by determining the absolute scattering intensity using, e.g., water scattering. In both cases, knowledge about the solute concentration and about the partial specific volume of the protein is required. By measuring 13 well characterized globular proteins with MMs ranging from 13.7 to 669 kDa we analyze the sources of possible systematic deviations and assess the accuracy of MM determination using SAXS. The data indicate that all these proteins have approximately the same `effective' value of the partial specific volume of about 0.7425 cm3 g−1. It is shown that both inter-protein and water calibration can be used for molecular mass determination by SAXS and in most cases the errors do not exceed 10%.
366 citations
TL;DR: The basic principles of SAXS are presented and a recently developed Ensemble Optimization Method (EOM) is now available that allows for the co-existence of multiple protein conformations in solution compatible with the scattering data.
Abstract: Small-angle scattering of X-rays (SAXS) is an established method to study the overall structure and structural transitions of biological macromolecules in solution. For folded proteins, the technique provides three-dimensional low resolution structures ab initio or it can be used to drive rigid-body modeling. SAXS is also a powerful tool for the quantitative analysis of flexible systems, including intrinsically disordered proteins (IDPs), and is highly complementary to the high resolution methods of X-ray crystallography and NMR. Here we present the basic principles of SAXS and review the main approaches to the characterization of IDPs and flexible multidomain proteins using SAXS. Together with the standard approaches based on the analysis of overall parameters, a recently developed Ensemble Optimization Method (EOM) is now available. The latter method allows for the co-existence of multiple protein conformations in solution compatible with the scattering data. Analysis of the selected ensembles provides quantitative information about flexibility and also offers insights into structural features. Examples of the use of SAXS and combined approaches with NMR, X-ray crystallography, and computational methods to characterize completely or partially disordered proteins are presented.
320 citations
TL;DR: The small-angle scattering biological data bank (SASBDB) has been designed in accordance with the plans of the SAStf as part of a future federated system of databases for biological SAXS and SANS.
Abstract: Small-angle X-ray and neutron scattering (SAXS and SANS) are fundamental tools used to study the global shapes of proteins, nucleic acids, macromolecular complexes and assemblies in solution. Due to recent advances in instrumentation and computational methods, the quantity of experimental scattering data and subsequent publications is increasing dramatically. The need for a global repository allowing investigators to locate and access experimental scattering data and associated models was recently emphasized by the wwPDB small-angle scattering task force (SAStf). The small-angle scattering biological data bank (SASBDB) www.sasbdb.org has been designed in accordance with the plans of the SAStf as part of a future federated system of databases for biological SAXS and SANS. SASBDB is a comprehensive repository of freely accessible and fully searchable SAS experimental data and models that are deposited together with the relevant experimental conditions, sample details and instrument characteristics. At present the quality of deposited experimental data and the accuracy of models are manually curated, with future plans to integrate automated systems as the database expands.
273 citations
TL;DR: The application of Tikhonov's regularization method for the solution of ill-posed problems in small-angle-scattering-data treatment is considered in this article, where simple regularization algorithms are proposed for solving convolution equations in data desmearing (slitwidth and polychromaticity problems) as well as for polydispersity problems.
Abstract: The application of Tikhonov's regularization method [Tikhonov & Arsenin (1977) Solution of Ill-Posed Problems New York: Wiley] for the solution of ill-posed problems in small-angle-scattering-data treatment is considered Simple regularization algorithms are proposed for solving convolution equations in data desmearing (slit-width and polychromaticity problems) as well as for polydispersity problems A general indirect approach of data processing based on the regularization method is described Comparison with other data-treatment methods is made
271 citations
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01 May 1993
TL;DR: Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems.
Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.
29,323 citations
28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: A review of gold nanoparticles can be found in this article, where the most stable metal nanoparticles, called gold colloids (AuNPs), have been used for catalysis and biology applications.
Abstract: Although gold is the subject of one of the most ancient themes of investigation in science, its renaissance now leads to an exponentially increasing number of publications, especially in the context of emerging nanoscience and nanotechnology with nanoparticles and self-assembled monolayers (SAMs). We will limit the present review to gold nanoparticles (AuNPs), also called gold colloids. AuNPs are the most stable metal nanoparticles, and they present fascinating aspects such as their assembly of multiple types involving materials science, the behavior of the individual particles, size-related electronic, magnetic and optical properties (quantum size effect), and their applications to catalysis and biology. Their promises are in these fields as well as in the bottom-up approach of nanotechnology, and they will be key materials and building block in the 21st century. Whereas the extraction of gold started in the 5th millennium B.C. near Varna (Bulgaria) and reached 10 tons per year in Egypt around 1200-1300 B.C. when the marvelous statue of Touthankamon was constructed, it is probable that “soluble” gold appeared around the 5th or 4th century B.C. in Egypt and China. In antiquity, materials were used in an ecological sense for both aesthetic and curative purposes. Colloidal gold was used to make ruby glass 293 Chem. Rev. 2004, 104, 293−346
11,752 citations
TL;DR: A new method, based on chemical thermodynamics, is developed for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments, as found, biological units may be recovered at 80-90% success rate, which makesX-ray crystallography an important source of experimental data on macromolescular complexes and protein-protein interactions.
8,377 citations