Capranico G.,University of Bologna |
Marinello J.,University of Bologna |
Journal of Medicinal Chemistry | Year: 2017
DNA topoisomerases constitute a large family of enzymes that are essential for all domains of life. Although they share general reaction chemistry and the capacity to govern DNA topology and resolve strand entanglements during fundamental molecular processes, they are characterized by differences in their structural organization, modes of enzymatic catalysis, and biological functions. Moreover, hundreds of compounds interfere with bacterial and/or eukaryotic enzymes, some of which are effective drugs for the treatment of infectious diseases and cancers. Research over the past decade has focused on the biological functions of DNA topoisomerases, and several findings have revealed unexpected roles of type I DNA topoisomerases, a subclass of these enzymes, in regulating gene expression and DNA and chromatin conformations. These new findings highlight that type I topoisomerases are still interesting targets for drug discovery for the treatment of several human diseases, including multidrug-resistant infections and genetic disorders. © 2017 American Chemical Society.
Baftizadeh F.,International School for Advanced Studies |
Biarnes X.,Ramon Llull University |
Pietrucci F.,Ecole Polytechnique Federale de Lausanne |
Affinito F.,CINECA |
Laio A.,International School for Advanced Studies
Journal of the American Chemical Society | Year: 2012
Starting from a disordered aggregate, we have simulated the formation of ordered amyloid-like beta structures in a system formed by 18 polyvaline chains in explicit solvent, employing molecular dynamics accelerated by bias-exchange metadynamics. We exploited 8 different collective variables to compute the free energy of hundreds of putative aggregate structures, with variable content of parallel and antiparallel β-sheets and different packing among the sheets. This allowed characterizing in detail a possible nucleation pathway for the formation of amyloid fibrils: first the system forms a relatively large ordered nucleus of antiparallel β-sheets, and then a few parallel sheets start appearing. The relevant nucleation process culminates at this point: when a sufficient number of parallel sheets is formed, the free energy starts to decrease toward a new minimum in which this structure is predominant. The complex nucleation pathway we found cannot be described within classical nucleation theory, namely employing a unique simple reaction coordinate like the total content of β-sheets. © 2012 American Chemical Society.
Azadi S.,International School for Advanced Studies |
Cavazzoni C.,CINECA |
Sorella S.,International School for Advanced Studies |
Sorella S.,CNR Institute of Materials
Physical Review B - Condensed Matter and Materials Physics | Year: 2010
We introduce a method for solving a self-consistent electronic calculation within localized atomic orbitals that allows us to converge to the complete basis set (CBS) limit in a stable, controlled, and systematic way. We compare our results with the ones obtained with a standard quantum chemistry package for the simple benzene molecule. We find perfect agreement for small basis set and show that, within our scheme, it is possible to work with a very large basis in an efficient and stable way. Therefore we can avoid to introduce any extrapolation to reach the CBS limit. In our study we have also carried out variational Monte Carlo and lattice regularized diffusion Monte Carlo with a standard many-body wave function defined by the product of a Slater determinant and a Jastrow factor. Once the Jastrow factor is optimized by keeping fixed the Slater determinant provided by our scheme, we obtain a very good description of the atomization energy of the benzene molecule only when the basis of atomic orbitals is large enough and close to the CBS limit, yielding the lowest variational energies. © 2010 The American Physical Society.
Bernaschi M.,CNR Institute of Neuroscience |
Bisson M.,CNR Institute of Neuroscience |
Computer Physics Communications | Year: 2014
We present and compare the performances of two many-core architectures: the Nvidia Kepler and the Intel MIC both in a single system and in cluster configuration for the simulation of spin systems. As a benchmark we consider the time required to update a single spin of the 3D Heisenberg spin glass model by using the Over-relaxation algorithm. We present data also for a traditional high-end multi-core architecture: the Intel Sandy Bridge. The results show that although on the two Intel architectures it is possible to use basically the same code, the performances of a Intel MIC change dramatically depending on (apparently) minor details. Another issue is that to obtain a reasonable scalability with the Intel Phi coprocessor (Phi is the coprocessor that implements the MIC architecture) in a cluster configuration it is necessary to use the so-called offload mode which reduces the performances of the single system. As to the GPU, the Kepler architecture offers a clear advantage with respect to the previous Fermi architecture maintaining exactly the same source code. Scalability of the multi-GPU implementation remains very good by using the CPU as a communication co-processor of the GPU. All source codes are provided for inspection and for double-checking the results. © 2014 Elsevier B.V. All rights reserved.
D'Annessa I.,University of Rome Tor Vergata |
Coletta A.,University of Rome Tor Vergata |
Sutthibutpong T.,University of Leeds |
Mitchell J.,Institute of Cancer Research |
And 3 more authors.
Nucleic Acids Research | Year: 2014
Human topoisomerase 1B has been simulated covalently bound to a negatively supercoiled DNA minicircle, and its behavior compared to the enzyme bound to a simple linear DNA duplex. The presence of the more realistic supercoiled substrate facilitates the formation of larger number of protein-DNA interactions when compared to a simple linear duplex fragment. The number of protein-DNA hydrogen bonds doubles in proximity to the active site, affecting all of the residues in the catalytic pentad. The clamp over the DNA, characterized by the salt bridge between Lys369 and Glu497, undergoes reduced fluctuations when bound to the supercoiled minicircle. The linker domain of the enzyme, which is implicated in the controlled relaxation of superhelical stress, also displays an increased number of contacts with the minicircle compared to linear DNA. Finally, the more complex topology of the supercoiled DNA minicircle gives rise to a secondary DNA binding site involving four residues located on subdomain III. The simulation trajectories reveal significant changes in the interactions between the enzyme and the DNA for the more complex DNA topology, which are consistent with the experimental observation that the protein has a preference for binding to supercoiled DNA. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Bernaschi M.,CNR Institute of Neuroscience |
Proceedings of the 2014 International Conference on High Performance Computing and Simulation, HPCS 2014 | Year: 2014
We present and compare the performances of two many-core architectures: the Nvidia Kepler and the Intel MIC both in a single system and in cluster configuration for the simulation of two physical systems. As a first benchmark we consider the time required to update a single spin of the 3D Heisenberg spin glass model by using the Over-relaxation algorithm. The second application we consider is a reactive fluid-dynamics problem for which we resolve the full Navier-Stokes compressible set of equations without resorting to a turbulence model. The results show that the performances of an Intel MIC change dramatically depending on (apparently) minor details. Another issue is that to obtain a reasonable scalability with the Intel Phi coprocessor in cluster configuration it is necessary to use the so-called offload mode which reduces the performances of the single system. All source codes are provided for inspection and for double-checking the results. © 2014 IEEE.
Vazza F.,National institute for astrophysics |
Brunetti G.,National institute for astrophysics |
Gheller C.,CINECA |
New Astronomy | Year: 2010
We present a sample of 20 massive galaxy clusters with total virial masses in the range of 6 × 10 14 M ⊙ ≤ M vir ≤ 2 × 10 15 M ⊙, re-simulated with a customized version of the 1.5. ENZO code employing adaptive mesh refinement. This technique allowed us to obtain unprecedented high spatial resolution (≈25 kpc/h) up to the distance of ∼3 virial radii from the clusters center, and makes it possible to focus with the same level of detail on the physical properties of the innermost and of the outermost cluster regions, providing new clues on the role of shock waves and turbulent motions in the ICM, across a wide range of scales. In this paper, a first exploratory study of this data set is presented. We report on the thermal properties of galaxy clusters at z = 0. Integrated and morphological properties of gas density, gas temperature, gas entropy and baryon fraction distributions are discussed, and compared with existing outcomes both from the observational and from the numerical literature. Our cluster sample shows an overall good consistency with the results obtained adopting other numerical techniques (e.g. Smoothed Particles Hydrodynamics), yet it provides a more accurate representation of the accretion patterns far outside the cluster cores. We also reconstruct the properties of shock waves within the sample by means of a velocity-based approach, and we study Mach numbers and energy distributions for the various dynamical states in clusters, giving estimates for the injection of Cosmic Rays particles at shocks. The present sample is rather unique in the panorama of cosmological simulations of massive galaxy clusters, due to its dynamical range, statistics of objects and number of time outputs. For this reason, we deploy a public repository of the available data, accessible via web portal at http://data.cineca.it. © 2010 Elsevier B.V. All rights reserved.
Vazza F.,Jacobs University Bremen |
Vazza F.,National institute for astrophysics |
Brunetti G.,National institute for astrophysics |
Gheller C.,CINECA |
And 2 more authors.
Astronomy and Astrophysics | Year: 2011
We study the properties of chaotic motions in the intra cluster medium using a set of 20 galaxy clusters simulated with large dynamical range, using the adaptive mesh refinement code ENZO. The adopted setup allows us to study the spectral and spatial properties of turbulent motions in galaxy clusters with unprecedented detail, achieving an maximum available Reynolds number of the order of Re ∼ 500-1000 for the largest eddies. We investigated the correlations between the energy of these motions in the intra cluster medium and the dynamical state of the host systems. We find that the statistical properties of turbulent motions and their evolution with time imply that major merger events are responsible for the injection of the bulk of turbulent kinetic energy into the cluster. Turbulence is found to account for ∼20-30 per cent of the thermal energy in merging clusters, and ∼5 per cent in relaxed clusters. We compare the energies of turbulence and motions in our simulated clusters with upper-limits for real nearby clusters derived from XMM-Newton data. When turbulent motions are compared on the same spatial scales, the data from simulations are well within the range presently allowed by observations. Finally, we comment on the possibility that turbulence may accelerate relativistic particles leading to the formation of giant radio halos in turbulent (merging) clusters. On the basis of our simulations, we confirm the conclusions of previous semi-analytical studies that the fraction of turbulent clusters appears to be consistent with that of clusters hosting radio halos. © 2011 ESO.
News Article | November 14, 2016
SALT LAKE CITY--(BUSINESS WIRE)--Celebrating its success in high-performance computing (HPC), Lenovo (SEHK:0992) today announced the completion of its second phase deployment at CINECA — a world class HPC research resource with the capabilities to become a leading artificial intelligence compute resource. The company also strengthened its position in the high performance computing space maintaining its #1 HPC vendor ranking in China while becoming the #2 vendor in the world in terms of total sy
News Article | December 24, 2015
Graduate students and postdoctoral scholars from institutions in Canada, Europe, Japan and the United States are invited to apply for the seventh International Summer School on HPC Challenges in Computational Sciences, to be held June 26 to July 1, 2016, in Ljubljana, Slovenia. Applications are due February 15, 2016. The summer school is sponsored by the Extreme Science and Engineering Discovery Environment (XSEDE) with funds from the U.S. National Science Foundation, Compute/Calcul Canada, the Partnership for Advanced Computing in Europe (PRACE) and the RIKEN Advanced Institute for Computational Science (RIKEN AICS). Leading American, European and Japanese computational scientists and HPC technologists will offer instruction on a variety of topics, including: The expense-paid program will benefit advanced scholars from Canadian, European, Japanese and U.S. institutions who use HPC to conduct research. Interested students should apply by February 15, 2016. Meals and housing will be covered for the selected participants, also travel from outside Europe. Applications from graduate students and postdocs in all science and engineering fields are welcome. Preference will be given to applicants with parallel programming experience, and a research plan that will benefit from the utilization of high performance computing systems. Compute Canada, in partnership with regional organizations ACENET, Calcul Québec, Compute Ontario and WestGrid, leads the acceleration of research innovation by deploying state-of-the-art advanced research computing (ARC) systems, storage and software solutions. Together they provide essential ARC services and infrastructure for Canadian researchers and their collaborators in all academic and industrial sectors. The Partnership for Advanced Computing in Europe (PRACE) is an international non-profit association with its seat in Brussels. The PRACE Research Infrastructure provides a persistent world-class high performance computing service for scientists and researchers from academia and industry in Europe. The computer systems and their operations accessible through PRACE are provided by 4 PRACE members (BSC representing Spain, CINECA representing Italy, GCS representing Germany and GENCI representing France). RIKEN is one of Japan’s largest research organizations with institutes and centers in locations throughout Japan. The Advanced Institute for Computational Science (AICS) strives to create an international center of excellence dedicated to generating world-leading results through the use of its world-class supercomputer ”K computer.” It serves as the core of the “innovative high-performance computer infrastructure” project promoted by the Ministry of Education, Culture, Sports, Science and Technology. The Extreme Science and Engineering Discovery Environment (XSEDE) is the most advanced, powerful and robust collection of integrated digital resources and services in the world. It is a single virtual system that scientists can use to interactively share computing resources, data and expertise. XSEDE accelerates scientific discovery by enhancing the productivity of researchers, engineers and scholars by deepening and extending the use of XSEDE¹s ecosystem of advanced digital services and by advancing and sustaining the XSEDE advanced digital infrastructure. XSEDE is a five-year, $121-million project and is supported by the National Science Foundation.