Physical Sciences and Mathematics Commons^™

Model File Name: Rna-Short-Helix.X3d, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: RNA-short-helix.x3d

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a DNA helix in which the atoms are colored by heteroatom (PDB: 1lmb). This model is designed to go with a teaching module comparing DNA and RNA basic structures and functions. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “RNA helix - polynucleotide molecule”. This model has been printed successfully using these parameters on Shapeways’ binder jetting printer in the Coated Full Color Sandstone material.

Video Guide To Design Flexible Dna.Mp4, Michelle Howell, Karin V. Van Dijk, Christine S. Booth, Tomáš Helikar, Brian Couch, Rebecca Roston

3-D Printed Model Structural Files

Model file name: Video guide to design flexible DNA.mp4

Authors: Michelle E Howell, Karin van Dijk, Christine S Booth, Tomas Helikar, Brian A Couch, Rebecca L Roston

This 30-minute video includes step-by-step instructions to design and 3-D print a long flexible DNA model that mimics the structure and function of DNA. The instructions are applicable for designing the model using open-source 3-D computer graphics software Blender 2.79 which is available for download at https://www.blender.org/download/.

.mp4 file download (70 MB) below.

Model File Name: Ssrna.Stl, Michelle Howell, Karin V. Van Dijk, Rebecca Roston

3-D Printed Model Structural Files

Model file name: ssRNA.stl

Authors: Michelle E Howell, Karin van Dijk, Rebecca L Roston

This is a teaching model of a single stranded piece of RNA in stick representation (PDB: 1ehz). This model is designed to go with a teaching module comparing DNA and RNA basic structures and functions. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “ssRNA”. This model has been printed successfully using these parameters on Shapeways’ laser sintering printer in the Elasto Plastic material.

Model File Name: Helix_H2o_Sphere2.Dae, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

Model file name: Helix_H2O_sphere2.dae

Authors: Michelle E Howell, Rebecca L Roston

This is a teaching model of a space fill representation of a protein α-helix (PDB: 3vjo). A space fill water molecule is also represented to illustrate the lack of space down the axis of an α-helix. This model can accompany a corresponding stick representation, a kinked α-helix, and a β-sheet. This model is designed to accompany a teaching module illustrating protein secondary structure and function. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Helix and Water (Space-fill) …

Model File Name: Beta-Sheet_Rod 0.7.Dae, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

Model file name: beta-sheet_rod 0.7.dae

Authors: Michelle E Howell, Rebecca L Roston

This is a teaching model of a stick representation of a protein β-sheet (PDB: 3vjo). This model is designed to accompany three other α-helix models: a space-fill representation of a straight α-helix, a stick representation of a straight α-helix, and a stick representation of a kinked α-helix. These models accompany a teaching module illustrating protein secondary structure and function. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Beta-sheet_Thick”. This model has been printed successfully using …

Model File Name: Alpha Helix Pro-Gly 0.7.Dae, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

Model file name: alpha helix pro-gly 0.7.dae

Authors: Michelle E Howell, Rebecca L Roston

This is a teaching model of a stick representation of a protein α-helix with proline and glycine residues highlighted (PDB: 3vjo). This model is designed to accompany a straight α-helix in space fill representation, a straight α-helix in stick representation, and a stick β-sheet model as well as a teaching module illustrating protein secondary structure and function. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Alpha Helix_Pro-Gly”. This model has been printed successfully using these parameters …

Model File Name: Alpha Helix 0.7.Dae, Michelle Howell, Rebecca Roston

3-D Printed Model Structural Files

Model file name: alpha helix 0.7.dae

Authors: Michelle E Howell, Rebecca L Roston

This is a teaching model of a stick representation of a protein α-helix (PDB: 3vjo). This model can accompany a corresponding space fill representation, a kinked α-helix, and a β-sheet. These models were designed to accompany a teaching module illustrating protein secondary structure and function. The printable model is already uploaded to Shapeways.com in the MacroMolecules shop under the name “Alpha Helix_Thick”. This model has been printed successfully using these parameters on Shapeways’ binder jetting printer in the Coated Full Color …

An Investigation Of Atomic Structures Derived From X-Ray Crystallography And Cryo-Electron Microscopy Using Distal Blocks Of Side-Chains, Lin Chen, Jing He, Salim Sazzed, Rayshawn Walker

Computer Science Faculty Publications

Cryo-electron microscopy (cryo-EM) is a structure determination method for large molecular complexes. As more and more atomic structures are determined using this technique, it is becoming possible to perform statistical characterization of side-chain conformations. Two data sets were involved to characterize block lengths for each of the 18 types of amino acids. One set contains 9131 structures resolved using X-ray crystallography from density maps with better than or equal to 1.5 Å resolutions, and the other contains 237 protein structures derived from cryo-EM density maps with 2-4 Å resolutions. The results show that the normalized probability density function of block …

Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz

Chemistry: Faculty Publications and Other Works

The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to …

Superhero Robotics, Frank Sup, Brian Umberger, Nick Sawyer

Science and Engineering Saturday Seminars

No abstract provided.

A Study Of Defensive Mechanisms Employed By Two Species Of Nudibranchs Using Toxicity And Unpalatability Analyses, Sean Youn

Independent Study Project (ISP) Collection

Nudibranchs are marine invertebrates that have developed an intriguing defense mechanism, including warning coloration and the use of chemicals accumulated through their sponge diet. The goal of this study was to determine whether the strength of chemical defenses differs between dietary and accumulated secondary metabolites for two species: Glossodoris vespa and Ceratosoma brevicaudatum. First, NMR spectroscopy was used to not only identify specific compounds in the mantle (outer covering) and the viscera (gut) but also to analyze the possibility of nudibranch species transporting more toxic compounds for defensive purposes. Next, toxicity (brine shrimp) and palatability (Palaemon shrimp) assays were used …

Data Publication With The Structural Biology Data Grid Supports Live Analysis, Peter A. Meyer, Stephanie Socias, Jason Key, Elizabeth Ransey, Emily C. Tjon, Alejandro Buschiazzo, Ming Lei, Chris Botka, James Withrow, David Neau, Kanagalaghatta Rajashankar, Karen S. Anderson, Richard H. Baxter, Stephen C. Blacklow, Titus J. Boggon, Alexandre M. J. J. Bonvin, Dominika Borek, Tom J. Brett, Amedeo Caflisch, Chung-I Chang, Walter J. Chazin, Kevin D. Corbett, Michael S. Cosgrove, Sean Crosson, Sirano Dhe-Paganon, Enrico Di Cera, Catherine L. Drennan, Michael J. Eck, Brandt F. Eichman, Qing R. Fan, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the …

Clique Topology Reveals Intrinsic Geometric Structure In Neural Correlations, Chad Giusti, Eva Pastalkova, Carina Curto, Vladimir Itskov

Department of Mathematics: Faculty Publications

Detecting meaningful structure in neural activity and connectivity data is challenging in the presence of hidden nonlinearities, where traditional eigenvalue-based methods may be misleading. We introduce a novel approach to matrix analysis, called clique topology, that extracts features of the data invariant under nonlinear monotone transformations. These features can be used to detect both random and geometric structure, and depend only on the relative ordering of matrix entries. We then analyzed the activity of pyramidal neurons in rat hippocampus, recorded while the animal was exploring a 2D environment, and confirmed that our method is able to detect geometric organization using …

Utilizing Nmr Spectroscopy And Molecular Docking As Tools For The Structural Determination And Functional Annotation Of Proteins, Jaime Stark

Department of Chemistry: Dissertations, Theses, and Student Research

With the completion of the Human Genome Project in 2001 and the subsequent explosion of organisms with sequenced genomes, we are now aware of nearly 28 million proteins. Determining the role of each of these proteins is essential to our understanding of biology and the development of medical advances. Unfortunately, the experimental approaches to determine protein function are too slow to investigate every protein. Bioinformatics approaches, such as sequence and structure homology, have helped to annotate the functions of many similar proteins. However, despite these computational approaches, approximately 40% of proteins still have no known function. Alleviating this deficit will …

Secondary Structure, A Missing Component Of Sequence- Based Minimotif Definitions, David P. Sargeant, Michael R. Gryk, Mark W. Maciejewsk, Vishal Thapar, Vamsi Kundeti, Sanguthevar Rajasekaran, Pedro Romero, Keith Dunker, Shun-Cheng Li, Tomonori Kaneko, Martin Schiller

Life Sciences Faculty Research

Minimotifs are short contiguous segments of proteins that have a known biological function. The hundreds of thousands of minimotifs discovered thus far are an important part of the theoretical understanding of the specificity of protein-protein interactions, posttranslational modifications, and signal transduction that occur in cells. However, a longstanding problem is that the different abstractions of the sequence definitions do not accurately capture the specificity, despite decades of effort by many labs. We present evidence that structure is an essential component of minimotif specificity, yet is not used in minimotif definitions. Our analysis of several known minimotifs as case studies, analysis …

Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller

Life Sciences Faculty Research

The low complexity of minimotif patterns results in a high false-positive prediction rate, hampering protein function prediction. A multi-filter algorithm, trained and tested on a linear regression model, support vector machine model, and neural network model, using a large dataset of verified minimotifs, vastly improves minimotif prediction accuracy while generating few false positives. An optimal threshold for the best accuracy reaches an overall accuracy above 90%, while a stringent threshold for the best specificity generates less than 1% false positives or even no false positives and still produces more than 90% true positives for the linear regression and neural network …

Evolution Of Spur-Length Diversity In Aquilegia Petals Is Achieved Solely Through Cell-Shape Anisotropy, Joshua R. Puzey, Sharon J. Gerbode, Scott A. Hodges, Elena M. Kramer, L. Mahadevan

All HMC Faculty Publications and Research

The role of petal spurs and specialized pollinator interactions has been studied since Darwin. Aquilegia petal spurs exhibit striking size and shape diversity, correlated with specialized pollinators ranging from bees to hawkmoths in a textbook example of adaptive radiation. Despite the evolutionary significance of spur length, remarkably little is known about Aquilegia spur morphogenesis and its evolution. Using experimental measurements, both at tissue and cellular levels, combined with numerical modelling, we have investigated the relative roles of cell divisions and cell shape in determining the morphology of the Aquilegia petal spur. Contrary to decades-old hypotheses implicating a discrete meristematic zone …

Scireader Enables Reading Of Medical Content With Instantaneous Definitions, Patrick R. Gradie, Megan Litster, Rinu Thomas, Jay Vyas, Martin Schiller

Life Sciences Faculty Research

Background

A major problem patients encounter when reading about health related issues is document interpretation, which limits reading comprehension and therefore negatively impacts health care. Currently, searching for medical definitions from an external source is time consuming, distracting, and negatively impacts reading comprehension and memory of the material.

Methods

SciReader was built as a Java application with a Flex-based front-end client. The dictionary used bySciReader was built by consolidating data from several sources and generating new definitions with a standardized syntax. The application was evaluated by measuring the percentage of words defined in different documents. A survey was used …

Pharmacological Chaperoning In Fabry Disease, Jerome Rogich

Masters Theses 1911 - February 2014

Fabry Disease is an X-­‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-­‐ Galactosidase A (α-­GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-­‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. …

Partitioning Of Minimotifs Based On Function With Improved Prediction Accuracy, Sanguthevar Rajasekaran, Tian Mi, Jerlin Camilus Merlin, Aaron Oommen, Patrick R. Gradie, Martin R. Schiller

Life Sciences Faculty Research

Background

Minimotifs are short contiguous peptide sequences in proteins that are known to have a function in at least one other protein. One of the principal limitations in minimotif prediction is that false positives limit the usefulness of this approach. As a step toward resolving this problem we have built, implemented, and tested a new data-driven algorithm that reduces false-positive predictions.

Methodology/Principal Findings

Certain domains and minimotifs are known to be strongly associated with a known cellular process or molecular function. Therefore, we hypothesized that by restricting minimotif predictions to those where the minimotif containing protein and target protein have …

Venn, A Tool For Titrating Sequence Conservation Onto Protein Structures, Jay Vyas, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

Residue conservation is an important, established method for inferring protein function, modularity and specificity. It is important to recognize that it is the 3D spatial orientation of residues that drives sequence conservation. Considering this, we have built a new computational tool, VENN that allows researchers to interactively and graphically titrate sequence homology onto surface representations of protein structures. Our proposed titration strategies reveal critical details that are not readily identified using other existing tools. Analyses of a bZIP transcription factor and receptor recognition of Fibroblast Growth Factor using VENN revealed key specificity determinants. Weblink: http://sbtools.uchc.edu/venn/.

A Proposed Syntax For Minimotif Semantics, Version 1., Jay Vyas, Ronald J. Nowling, Mark W. Maciejewski, Sanguthevar Rajasekaran, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

BACKGROUND:

One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of …

Geometric Build-Up Solutions For Protein Determination Via Distance Geometry, Robert Tucker Davis

Masters Theses & Specialist Projects

Proteins carry out an almost innumerable amount of biological processes that are absolutely necessary to life and as a result proteins and their structures are very often the objects of study in research. As such, this thesis will begin with a description of protein function and structure, followed by brief discussions of the two major experimental structure determination methods. Another problem that often arises in molecular modeling is referred to as the Molecular Distance Geometry Problem (MDGP). This problem seeks to find coordinates for the atoms of a protein or molecule when given only a set of pair-wise distances between …

Minimotif Miner 2nd Release: A Database And Web System For Motif Search, Sanguthevar Rajasekaran, Sudha Balla, Patrick R. Gradie, Michael R. Gryk, Krishna Kadaveru, Vamsi Kundeti, Mark W. Maciejewski, Tian Mi, Nicholas Rubino, Jay Vyas, Martin R. Schiller

Life Sciences Faculty Research

Minimotif Miner (MnM) consists of a minimotif database and a web-based application that enables prediction of motif-based functions in user-supplied protein queries. We have revised MnM by expanding the database more than 10-fold to approximately 5000 motifs and standardized the motif function definitions. The web-application user interface has been redeveloped with new features including improved navigation, screencast-driven help, support for alias names and expanded SNP analysis. A sample analysis of prion shows how MnM 2 can be used.

Dynamics Of Apomyoglobin In The Α-To-Β Transition And Of Partially Unfolded Aggregated Protein, E. Fabiani, A. M. Stadler, D. Madern, M. M. Koza, M. Tehei, M. Hirai, G. Zaccai

Faculty of Science - Papers (Archive)

Changes of molecular dynamics in the α-to-β transition associated with amyloid fibril formation were explored on apo-myoglobin (ApoMb) as a model system. Circular dichroism, neutron and X-ray scattering experiments were performed as a function of temperature on the protein, at different solvent conditions. A significant change in molecular dynamics was observed at the α-to-β transition at about 55 ˚C, indicating a more resilient high temperature β structure phase. A similar effect at approximately the same temperature was observed in holo-myoglobin, associated with partial unfolding and protein aggregation. A study in a wide temperature range between 20 K and 360 K …

Small Heat Shock Protein Activity Is Regulated By Variable Oligomeric Substructure, J. L. Benesch, M. Ayoub, C. V. Robinson, J. A. Aquilina

Faculty of Science - Papers (Archive)

The alpha-crystallins are members of the small heat shock protein (sHSP) family of molecular chaperones which have evolved to minimize intracellular protein aggregation, however they are also implicated in a number of protein deposition diseases. In this study we have employed novel mass spectrometry techniques to investigate the changes in quaternary structure associated with this switch from chaperone to adjuvant of aggregation. We have replicated the oligomeric rearrangements observed for in vivo disease-related modifications, without altering the protein sequence, by refolding the alpha-crystallins in vitro. This refolding results in a loss of dimeric substructure concomitant with an augmentation of substrate …

A Subgroup Algorithm To Identify Cross-Rotation Peaks Consistent With Non-Crystallographic Symmetry, Ryan H. Lilien, Chris Bailey-Kellogg, Amy C. Anderson, Bruce R. Donald

Dartmouth Scholarship

Molecular replacement (MR) often plays a prominent role in determining initial phase angles for structure determination by X-ray crystallography. In this paper, an efficient quaternion-based algorithm is presented for analyzing peaks from a cross-rotation function in order to identify model orientations consistent with proper non-crystallographic symmetry (NCS) and to generate proper NCS-consistent orientations missing from the list of cross-rotation peaks. The algorithm, CRANS, analyzes the rotation differences between each pair of cross-rotation peaks to identify finite subgroups. Sets of rotation differences satisfying the subgroup axioms correspond to orientations compatible with the correct proper NCS. The CRANS algorithm was first …