Using 3D printed physical models to monitor knowledge integration in biochemistry

2018 ◽  
Vol 19 (4) ◽  
pp. 1199-1215 ◽  
Author(s):  
Melissa A. Babilonia-Rosa ◽  
H. Kenny Kuo ◽  
Maria T. Oliver-Hoyo
Keyword(s):  
Small Molecules ◽  
Knowledge Integration ◽  
Noncovalent Interactions ◽  
Three Dimensional ◽  
Student Understanding ◽  
Physical Models ◽  
Dimensional Structure ◽  
Instructional Resources ◽  
3D Printed ◽  
Different Sources

Noncovalent interactions determine the three-dimensional structure of macromolecules and the binding interactions between molecules. Students struggle to understand noncovalent interactions and how they relate to structure–function relationships. Additionally, students’ difficulties translating from two-dimensional representations to three-dimensional representations add another layer of complexity found in macromolecules. Therefore, we developed instructional resources that use 3D physical models to target student understanding of noncovalent interactions of small molecules and macromolecules. To this effect, we monitored indicators of knowledge integration as evidenced in student-generated drawings. Analysis of the drawings revealed that students were able to incorporate relevant conceptual features into their drawings from different sources as well as present their understanding from different perspectives.

scholarly journals Protein Folding: Search for Basic Physical Models

2003 ◽  
Vol 3 ◽  
pp. 623-635 ◽  
Author(s):  
Ivan Y. Torshin ◽  
Robert W. Harrison
Keyword(s):  
Protein Folding ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Physical Models ◽  
Dimensional Structure ◽  
Computational Techniques ◽  
Linear Sequence ◽  
Physical Forces

How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context ofin vivoprotein folding (which has been studied only for a few proteins), the roles of the fundamental physical forces in thein vitrofolding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces). Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.

scholarly journals Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions

Amino Acids ◽  
2019 ◽  
Vol 51 (10-12) ◽  
pp. 1409-1431 ◽  
Author(s):  
Luigi Grassi ◽  
Chiara Cabrele
Keyword(s):  
Small Molecules ◽  
Three Dimensional ◽  
Drug Market ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Chemical Modifications ◽  
Small Molecule Drugs ◽  
And Function ◽  
The Impact

Abstract Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.

Physical Models as an Aid for Teaching Wood Anatomy

IAWA Journal ◽  
2011 ◽  
Vol 32 (3) ◽  
pp. 301-312 ◽  
Author(s):  
Barbara Lachenbruch
Keyword(s):  
Wood Anatomy ◽  
Three Dimensional ◽  
Microfibril Angle ◽  
Physical Models ◽  
Dimensional Structure ◽  
Annual Rings ◽  
Student Activities ◽  
Teaching Activities ◽  
Vessel Elements ◽  
And Function

Student activities and instructor-made models are described to facilitate and encourage other instructors to develop their own appropriate activities and models for teaching the three-dimensional structure of wood. The teaching activities include making several annual rings with straws pushed into clay, drawing wood’s structure onto a piece of paper that is folded to resemble a wedge, and assigning students to make an anatomical model to present in class. Plans are given for instructor-made models (1:500 scale) of tracheids, vessel elements, and a hardwood ‘fiber’ to demonstrate their relative dimensions and geometries. These models also include a set of outerwood and corewood tracheids onto which the microfibril angle is traced, and one tracheid on which bordered and cross-field pitting are shown. Plans are then given for a bordered pit pair with its membrane (1:6300 scale). The last model demonstrates the Hagen-Poiseuille equation with an array of 16 conduits that together have the same potential flow as one conduit of two times their diameter. The use of these models has enlivened the classroom and helped students to more readily grasp wood anatomy and function.

scholarly journals 2-amino-1,3-benzothiazole-6-carboxamide Preferentially Binds the Tandem Mismatch Motif r(UY:GA)

2020 ◽  
Author(s):  
Andrew T. Chang ◽  
Lu Chen ◽  
Luo Song ◽  
Shuxing Zhang ◽  
Edward P. Nikonowicz
Keyword(s):  
Small Molecules ◽  
Dipolar Coupling ◽  
Residual Dipolar Coupling ◽  
Three Dimensional ◽  
Coupling Constants ◽  
Dimensional Structure ◽  
Flanking Sequence ◽  
Base Pairs ◽  
Virtual Screen ◽  
Rna Hairpin

AbstractRNA helices are often punctuated with non-Watson-Crick features that can be the target of chemical compounds, but progress towards identifying small molecules specific for non-canonical elements has been slow. We have used a tandem UU:GA mismatch motif (5’-UG-3’:5’-AU-3’) embedded within the helix of an RNA hairpin as a model to identify compounds that bind the motif specifically. The three-dimensional structure of the RNA hairpin and its interaction with a small molecule compound identified through a virtual screen are presented. The G-A of the mismatch forms a sheared pair upon which the U-U base pair stacks. The hydrogen bond configuration of the U-U pair involves the O2 of the U adjacent to the G and the O4 of the U adjacent to the A. The G-A and U-U pairs are flanked by A-U and G-C base pairs, respectively, and the mismatch exhibits greater stability than when the motif is within the context of other flanking base pairs or when the 5’-3’ orientation of the G-A and U-U is swapped. Residual dipolar coupling constants were used to generate an ensemble of structures against which a virtual screen of 64,480 small molecules was performed to identify candidate compounds that the motif specifically binds. The tandem mismatch was found to be specific for one compound, 2-amino-1,3-benzothiazole-6-carboxamide, which binds with moderate affinity but extends the motif to include the flanking A-U and G-C base pairs. The finding that affinity for the UU:GA mismatch is flanking sequence dependent emphasizes the importance of motif context and potentially increases the number of small non-canonical features within RNA that can be specifically targeted by small molecules.

scholarly journals 3D-printed drug testing platform based on a 3D model of aged human skeletal muscle

2020 ◽  
Author(s):  
Rafael Mestre ◽  
Nerea García ◽  
Tania Patiño ◽  
Maria Guix ◽  
Mauricio Valerio-Santiago ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Disease Modeling ◽  
Force Measurement ◽  
Muscle Relaxation ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Muscular Tissue ◽  
Functional Changes ◽  
3D Printed

AbstractThree-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aged or senescence-like tissue, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

scholarly journals Cryo-electron Microscopy and Exploratory Antisense Targeting of the 28-kDa Frameshift Stimulation Element from the SARS-CoV-2 RNA Genome

2020 ◽  
Author(s):  
Kaiming Zhang ◽  
Ivan N. Zheludev ◽  
Rachel J. Hagey ◽  
Marie Teng-Pei Wu ◽  
Raphael Haslecker ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Small Molecules ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Locked Nucleic Acid ◽  
Dimensional Structure ◽  
Potential Candidate ◽  
Cryo Electron Microscopy ◽  
Rna Genome ◽  
Cellular Replication

AbstractDrug discovery campaigns against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are beginning to target the viral RNA genome1, 2. The frameshift stimulation element (FSE) of the SARS-CoV-2 genome is required for balanced expression of essential viral proteins and is highly conserved, making it a potential candidate for antiviral targeting by small molecules and oligonucleotides3–6. To aid global efforts focusing on SARS-CoV-2 frameshifting, we report exploratory results from frameshifting and cellular replication experiments with locked nucleic acid (LNA) antisense oligonucleotides (ASOs), which support the FSE as a therapeutic target but highlight difficulties in achieving strong inactivation. To understand current limitations, we applied cryogenic electron microscopy (cryo-EM) and the Ribosolve7 pipeline to determine a three-dimensional structure of the SARS-CoV-2 FSE, validated through an RNA nanostructure tagging method. This is the smallest macromolecule (88 nt; 28 kDa) resolved by single-particle cryo-EM at subnanometer resolution to date. The tertiary structure model, defined to an estimated accuracy of 5.9 Å, presents a topologically complex fold in which the 5′ end threads through a ring formed inside a three-stem pseudoknot. Our results suggest an updated model for SARS-CoV-2 frameshifting as well as binding sites that may be targeted by next generation ASOs and small molecules.

scholarly journals Three-Dimensional Evaluation on Accuracy of Conventional and Milled Gypsum Models and 3D Printed Photopolymer Models

Materials ◽  
2019 ◽  
Vol 12 (21) ◽  
pp. 3499 ◽  
Author(s):  
Jae-Won Choi ◽  
Jong-Ju Ahn ◽  
Keunbada Son ◽  
Jung-Bo Huh
Keyword(s):  
Reference Model ◽  
Three Dimensional ◽  
Color Difference ◽  
Physical Models ◽  
The Other ◽  
3D Analysis ◽  
Digital Light Processing ◽  
Single Crown ◽  
Significant Difference ◽  
3D Printed

The aim of this study was to evaluate the accuracy of dental models fabricated by conventional, milling, and three-dimensional (3D) printing methods. A reference model with inlay, single crown, and three-unit fixed dental prostheses (FDP) preparations was prepared. Conventional gypsum models (CON) were manufactured from the conventional method. Digital impressions were obtained by intraoral scanner, which were converted into physical models such as milled gypsum models (MIL), stereolithography (SLA), and digital light processing (DLP) 3D printed photopolymer models (S3P and D3P). Models were extracted as standard triangulated language (STL) data by reference scanner. All STL data were superimposed by 3D analysis software and quantitative and qualitative analysis was performed using root mean square (RMS) values and color difference map. Statistical analyses were performed using the Kruskal–Wallis test and Mann–Whitney U test with Bonferroni’s correction. For full arch, the RMS value of trueness and precision in CON was significantly smaller than in the other groups (p < 0.05/6 = 0.008), and there was no significant difference between S3P and D3P (p > 0.05/6 = 0.008). On the other hand, the RMS value of trueness in CON was significantly smaller than in the other groups for all prepared teeth (p < 0.05/6 = 0.008), and there was no significant difference between MIL and S3P (p > 0.05/6 = 0.008). In conclusion, conventional gypsum models showed better accuracy than digitally milled and 3D printed models.

Three-Dimensional Structure of the Gap Junction Connexon and Intercellular Channel

1997 ◽  
Vol 3 (S2) ◽  
pp. 227-228
Author(s):  
Guy Perkins ◽  
Dan Goodenough ◽  
Gina Sosinsky
Keyword(s):  
Small Molecules ◽  
Gap Junction ◽  
Three Dimensional ◽  
Surface Topology ◽  
Dimensional Structure ◽  
Cell Contact ◽  
Membrane Channels ◽  
Membrane Channel ◽  
Contact Areas ◽  
Intercellular Channel

Gap junctions are specialized cell-cell contact areas by which cells communication with each other. Within these contact areas are tens to thousands of membrane channels. A gap junction membrane channel (also referred to as an intercellular channel) is unique among membrane channels in that it is composed of two oligomers with each of two adjacent tissue cells contributing one oligomer (called a connexon or hemichannel). The pore of the intercellular channel controls the passage of small molecules and ions from one cell to another.We are interested in how the structure and surface topology of the gap junction connexon at its extracellular surface influences the docking and formation of an intercellular communicating channel. It has been demonstrated that connexons made from some connexins will dock and form functional channels with some but not all connexons made from other isoforms. This selectivity is surprising considering that the primary sequences of the docking domains are highly conserved.

A Switched-Line Phase Shifter Fabricated with Additive Manufacturing

2013 ◽  
Vol 2013 (1) ◽  
pp. 000909-000913
Author(s):  
Jonathan M. O'Brien ◽  
Eduardo Rojas ◽  
Thomas M. Weller
Keyword(s):  
Additive Manufacturing ◽  
Material Properties ◽  
High Frequency ◽  
Phase Shifter ◽  
Ring Resonator ◽  
Three Dimensional ◽  
Equivalent Circuit Model ◽  
Structure Design ◽  
Dimensional Structure ◽  
3D Printed

Additive manufacturing, also known as 3D printing, has proven to be advantageous compared to conventional planar methods when utilizing the volume of a structure to miniaturize the design. The use of additive manufacturing can allow for high frequency circuitry to be conformed to an arbitrary shape while maintaining or enhancing performance. Recent advancements in low loss materials applicable to additive manufacturing have pushed performance levels even further. Utilizing additive manufacturing to build a three dimensional structure can improve factors such as reliability and repeatability by making the structure one solid piece as opposed to assembling multiple planar objects into the 3D shape. This allows the circuitry to be built around the structure. With this design approach other considerations, such as stability and strength, can be concentrated on during the structure design to realize new shapes. The purpose of this work is to investigate a 3D printed material, ULTEM, for radio frequency use and design a switched line phase shifter using the derived material properties. The first step in any high frequency circuit design is to have accurate material properties. An efficient way to determine the permittivity and loss tangent of a material is to place a ring resonator on the substrate and measure the resonant frequency and Q factor. An equivalent circuit model can then be built to match the measured response and the material properties extracted through circuit theory. From here accurate transmission line models can be analyzed to optimize the performance of the RF circuit. In this paper a ring resonator was designed on ULTEM to characterize the material properties. A 90° phase shifter was then fabricated on a 3D printed ULTEM substrate and a benchmark model was fabricated using traditional planar methods on Rogers RO4003C substrate. A comparison between the two models is given in this paper.

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