Dr. Bajaj and CVC had chance for a quick discussion with Bill Gates about Computational Accelera of Drug Discovery and Neurophysiome: Brain Connectomics and Function at the grand opening event of GDC.

The project overviews can be found . . . → Read More: CVC talked to Bill Gates]]>

Dr. Bajaj and CVC had chance for a quick discussion with Bill Gates about *Computational Accelera of Drug Discovery* and *Neurophysiome: Brain Connectomics and Function* at the grand opening event of GDC.

The project overviews can be found for:

Computational Accelera of Drug Discovery

Neurophysiome: Brain Connectomics and Function

Snapshot of Dr. Bajaj and Bill Gates in discussion (photo in CSEM facebook)

]]>A. Rand; A. Gillette; C. Bajaj Quadratic Serendipity Finite Elememts on Polygons using Genralized Barycentric Coordinates Mathematics for Computation, Accepted for Publication, 2013.

Abstract:
We introduce a nite element construction for use on the class of convex, planar polygons and show it obtains a quadratic error convergence estimate. On a convex . . . → Read More: Journal paper in Mathematics for Computation]]>

A. Rand; A. Gillette; C. Bajaj

Quadratic Serendipity Finite Elememts on Polygons using Genralized Barycentric Coordinates

Mathematics for Computation, Accepted for Publication, 2013.

Abstract:

We introduce a nite element construction for use on the class of convex, planar polygons and show it obtains a quadratic error convergence estimate. On a convex n-gon, our construction produces 2n basis functions, associated in a Lagrange-like fashion to each vertex and each edge midpoint, by transforming and combining a set of n(n+ 1) = 2 basis functions known

to obtain quadratic convergence. The technique broadens the scope of the so-called `serendipity’ elements, previously studied only for quadrilateral and regular hexahedral meshes, by employing the theory of generalized barycentric coordinates. Uniform a priori

error estimates are established over the class of convex quadrilaterals with bounded aspect ratio as well as over the class of convex planar polygons satisfying additional shape regularity conditions to exclude large interior angles and short edges. Numerical evidence is provided on a trapezoidal quadrilateral mesh, previously not amenable to serendipity

constructions, and applications to adaptive meshing are discussed.

Manuscript can be found from full list of publications

]]>Y. Hashem , A. Georges , J. Fu , S. Buss , F. Jossinet , A. Jobe , Q. Zhang , H. Liao , R. Grassucci , C. Bajaj , E. Westhof , S. Madison-Antenucci, J. Frank High-resolution cryo-EM structure of the unique Trypanosoma brucei 80S ribosome Nature, Feb. 2013, doi:10.1038/nature11872

Abstract:
Ribosomes, the . . . → Read More: Journal paper in Nature]]>

Y. Hashem , A. Georges , J. Fu , S. Buss , F. Jossinet , A. Jobe , **Q. Zhang** , H. Liao , R. Grassucci , **C. Bajaj** , E. Westhof , S. Madison-Antenucci, J. Frank

High-resolution cryo-EM structure of the unique Trypanosoma brucei 80S ribosome

Nature, Feb. 2013, doi:10.1038/nature11872

Abstract:

Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome [1, 2, 3, 4, 5, 6] reveal that it is more complex than its prokaryotic counterpart [7, 8], owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments9. The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids, unicellular eukaryotic parasites often infectious to humans. Here we present a high-resolution cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African sleeping sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large expansion segments and ribosomal-protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit (LSU) rRNA chain, which is known to be cleaved uniquely into six pieces [10, 11, 12], and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation-regulation process. The structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein-translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs

Manuscirpt can be found from Full list of publications

]]>Speakers: Muhibur Rasheed and Qiming Yuan

Title: Training F2Dock

F2Dock is a rigid body docking software which has a FFT based on-the-fly scoring scheme involving shape complementarity, electrostatics, simple charge complementarity and interface propensity, followed by a rescoring and reranking phase using proximity clustering, clash filter, Lennard-Jones filter, antibody filter, enzyme . . . → Read More: Training F2Dock]]>

Speakers: Muhibur Rasheed and Qiming Yuan

Title: Training F2Dock

F2Dock is a rigid body docking software which has a FFT based on-the-fly scoring scheme involving shape complementarity, electrostatics, simple charge complementarity and interface propensity, followed by a rescoring and reranking phase using proximity clustering, clash filter, Lennard-Jones filter, antibody filter, enzyme filter, residue contact filter, interface propensity filter, interface area filter etc. Overall there are more than 100 parameters in the scoring function. In the first part of the talk, we discuss all of these and explain the (mostly manual) strategy applied to train them. In the second part of the talk we explore several existing techniques for automated training of different types of parameters and evaluate their feasibility in training the parameters of F2Dock.

]]>Speaker: Maysam Moussalem

Title: A Reduced Flexibility Model for Macromolecules

Abstract: One of the biggest challenges in computational drug design is the need for accurate and efficient modeling and exploration of macromolecules’ large number of degrees of freedom, which would result in better pose prediction in lead optimization. In this talk, . . . → Read More: A Reduced Flexibility Model for Macromolecules]]>

Speaker: Maysam Moussalem

Title: A Reduced Flexibility Model for Macromolecules

Abstract: One of the biggest challenges in computational drug design is the need for accurate and efficient modeling and exploration of macromolecules’ large number of degrees of freedom, which would result in better pose prediction in lead optimization. In this talk, we present a reduced flexibility model for efficient exploration of relevant conformational space, allowing us to avoid exhaustive searches of all degrees of freedom while docking. An algorithm for detecting potential sites of flexibility using a knowledge-based approach is presented.

]]>Speaker: Radhakrishna Bettadapura

Title: Understanding shear in proteins

Abstract: Shear is lateral motion between a pair of protein interfaces. Though there are tens of proteins—and hundreds of accompanying interfaces— which are known to undergo shear, little is known about the shearing mechanism itself. Do a given pair of protein interfaces . . . → Read More: Understanding shear in proteins]]>

Speaker: Radhakrishna Bettadapura

Title: Understanding shear in proteins

Abstract: Shear is lateral motion between a pair of protein interfaces. Though there are tens of proteins—and hundreds of accompanying interfaces— which are known to undergo shear, little is known about the shearing mechanism itself. Do a given pair of protein interfaces undergo shear? If so, to what degree? These questions are currently difficult to answer.

My talk will be in two parts. In the first part, I will present a simple, planar shear parametrization; apply it to several helix-helix interfaces in citrate-synthase, comparing my results with those in the literature; and draw a few preliminary inferences. In the second part, I will present the results of applying shear to a docking exercise involving the SIV-17b complex and the D1D2 neutralizing antibody.

]]>Geometry in Compression Structures

Philippe Block, PhD Assistant Professor in Building Structure Institute of Technology in Architecture, ETH Zurich http://block.arch.ethz.ch

This lecture will present a new computational form finding method for exploring three-dimensional equilibrium networks, based on (re-)discovered understanding of the stability of the spectacular vaults from the Gothic. Through the use of intuitive . . . → Read More: Special Seminar: Geometry in Compression Structures]]>

**Geometry in Compression Structures **

Philippe Block, PhD

Assistant Professor in Building Structure

Institute of Technology in Architecture, ETH Zurich

http://block.arch.ethz.ch

This lecture will present a new computational form finding method for exploring three-dimensional equilibrium networks, based on (re-)discovered understanding of the stability of the spectacular vaults from the Gothic. Through the use of intuitive graphical diagrams, the presented approach now allows designers to gain control over the exploration of structural form, which starts to blur the boundaries between funicular (compression-only) and freeform design. Thanks to insights provided by dual geometrical relations, this innovative approach furthermore allowed to establish efficient solving algorithms for the nonlinear, inverse problem of form rationalization. These new extensions of this research have powerful applications not only for the design of freeform shells, but also for the equilibrium analysis of historical unreinforced masonry vaulted structures with complex geometries. The power of this geometry-driven form finding method will be demonstrated through several built prototypes at different scales, addressing challenges in tessellation, fabrication constraints, and efficiency in construction.

Short bio:

Philippe Block is Assistant Professor of Structural Design at ETH Zurich since 2009. He has multi-disciplinary research interests including graphical design and analysis techniques, computational form finding and optimization, and structural and architectural geometry. He obtained his PhD from MIT in 2009 for the development of a novel computational method for assessing the safety of historic vaulted structures in masonry and for designing efficient, freeform compression structures, awarded by e.g. the Hangai Prize from the International Association of Shell and Spatial Structures in 2007. Collaborating with architects and engineers, Block applies his research into practice for the structural assessment of historic monuments and the engineering of novel compression structures with projects ranging from unique vaults in cut stone to sustainable construction solutions for developing countries.

]]>Speaker: Muhibur Rasheed

Title: Multi-protein docking for viral capsids

Abstract:
Many biological functions are carried out by macromolecules or complexes composed of multiple proteins and nucleic acids. For example, the ribosome in E. Coli has 56 proteins, and viral capsids can be formed by hundreds of proteins. In this talk, we introduce . . . → Read More: Multi-protein docking for viral capsids]]>

Speaker: Muhibur Rasheed

Title: Multi-protein docking for viral capsids

Abstract:

Many biological functions are carried out by macromolecules or complexes composed of multiple proteins and nucleic acids. For example, the ribosome in E. Coli has 56 proteins, and viral capsids can be formed by hundreds of proteins. In this talk, we introduce the multi-protein docking problem as a tool to understand the structure, assembly and function of large complexes. The problem is NP-Hard in its most general formulation and hence researchers have made assumptions about the assembly process or restricted the problem to complexes having specific symmetries. We discuss current multi-protein docking techniques in terms of their search space, sampling technique and scoring functions and note that current techniques have many scopes for improvement. But we specifically choose the problem of viral capsid assembly due to its significance in anti-viral drug design. We discuss the current knowledge on the symmetry of the capsid structure and show how this symmetry can be applied to formulate a restricted class of multi-protein docking problem. We also show that how solutions of this problem can be used to identify leads for anti-viral drugs and to aid steady state analysis of assembly.

Speaker: Zhang Qin

Title: Ribosomal Protein Modeling for Trypanosoma Brucei from a 5.16A EM Density Map

Abstract As the protein-synthesis machine, the ribosome has been intensively researched including structure, function, evolution, genetics and dynamics during the past several decades. Compared to the prokaryotic ribosome, the eukaryotic ribosome is much larger and . . . → Read More: Ribosomal Protein Modeling for Trypanosoma Brucei from a 5.16A EM Density Map]]>

Speaker: Zhang Qin

Title: Ribosomal Protein Modeling for Trypanosoma Brucei from a 5.16A EM Density Map

Abstract As the protein-synthesis machine, the ribosome has been intensively researched including structure, function, evolution, genetics and dynamics during the past several decades. Compared to the prokaryotic ribosome, the eukaryotic ribosome is much larger and contains more complex RNA and proteins. This last decade has witnessed the progress of revealing eukaryotic ribosome structure by the cooperation of X-ray and cryo-EM technologies. In this talk, we will present the current status of ribosomal protein modeling for Trypanosoma Brucei from a high resolution EM density map. From the protein sequences, we will show the pipeline of homology modeling and models evaluation. Then partial results on flexible fitting of the protein models into the density map, segmentation and secondary structures detection for each protein will be reported. Challenges and problems will be addressed for further research. This is a collaborative research project with the J. Frank group.

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