scholarly journals DNA Nanodevices as Mechanical Probes of Protein Structure and Function

2021 ◽  
Vol 11 (6) ◽  
pp. 2802
Author(s):  
Nicholas Stephanopoulos ◽  
Petr Šulc
Keyword(s):  
Protein Structure ◽  
Protein Function ◽  
Cell Activation ◽  
Dna Nanotechnology ◽  
Future Directions ◽  
Precise Control ◽  
Wide Range ◽  
Promising Application ◽  
And Function

DNA nanotechnology has reported a wide range of structurally tunable scaffolds with precise control over their size, shape and mechanical properties. One promising application of these nanodevices is as probes for protein function or determination of protein structure. In this perspective we cover several recent examples in this field, including determining the effect of ligand spacing and multivalency on cell activation, applying forces at the nanoscale, and helping to solve protein structure by cryo-EM. We also highlight some future directions in the chemistry necessary for integrating proteins with DNA nanoscaffolds, as well as opportunities for computational modeling of hybrid protein-DNA nanomaterials.

scholarly journals Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Dna Nanotechnology ◽  
Biological Properties ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Nanoscale Structures ◽  
Immune Cell Activation ◽  
Wide Range ◽  
Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

scholarly journals Copper(I)-Catalyzed Click Chemistry as a Tool for the Functionalization of Nanomaterials and the Preparation of Electrochemical (Bio)Sensors

Sensors ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 2379 ◽  
Author(s):  
P. Yáñez-Sedeño ◽  
A. González-Cortés ◽  
S. Campuzano ◽  
J. M. Pingarrón
Keyword(s):  
Electrochemical Sensors ◽  
Functional Integration ◽  
Future Directions ◽  
Physiological Conditions ◽  
Electrode Surfaces ◽  
Wide Range ◽  
High Yields ◽  
By Products ◽  
Powerful Strategy

Proper functionalization of electrode surfaces and/or nanomaterials plays a crucial role in the preparation of electrochemical (bio)sensors and their resulting performance. In this context, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been demonstrated to be a powerful strategy due to the high yields achieved, absence of by-products and moderate conditions required both in aqueous medium and under physiological conditions. This particular chemistry offers great potential to functionalize a wide variety of electrode surfaces, nanomaterials, metallophthalocyanines (MPcs) and polymers, thus providing electrochemical platforms with improved electrocatalytic ability and allowing the stable, reproducible and functional integration of a wide range of nanomaterials and/or different biomolecules (enzymes, antibodies, nucleic acids and peptides). Considering the rapid progress in the field, and the potential of this technology, this review paper outlines the unique features imparted by this particular reaction in the development of electrochemical sensors through the discussion of representative examples of the methods mainly reported over the last five years. Special attention has been paid to electrochemical (bio)sensors prepared using nanomaterials and applied to the determination of relevant analytes at different molecular levels. Current challenges and future directions in this field are also briefly pointed out.

The T3 Method (“T3 It!”): Transcribe → Translate → Transform

2017 ◽  
Vol 79 (4) ◽  
pp. 257-271
Author(s):  
Brett Malas
Keyword(s):  
Protein Folding ◽  
Protein Structure ◽  
Differentiated Instruction ◽  
Genetic Information ◽  
Structural Models ◽  
Structure And Function ◽  
Protein Structure And Function ◽  
Learning Contexts ◽  
Wide Range ◽  
And Function

Traditional transcription-translation exercises are instructionally incomplete by failing to link prescriptive genetic information with protein structure and function. The T3 Method solves this problem by adding a conceptually powerful yet easily learned third step where students use simple protein folding codes to transform their translations into corresponding protein structural models. This brings structural sense to sequence and makes the information-to-proteins connection that is so profoundly important to understand in biology more directly evident, experiential, and intrinsically meaningful. The T3 Method has further utility, proving versatile and adaptive to a wide range of academic levels and learning contexts, with possibilities for differentiated instruction, application, and extension.

scholarly journals Prioritization of antimicrobial targets by CRISPR-based oligo recombineering

2021 ◽  
Author(s):  
HJ. Benns ◽  
M. Storch ◽  
J. Falco ◽  
FR. Fisher ◽  
E. Alves ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Function ◽  
Proof Of Concept ◽  
Fitness Effect ◽  
Diverse Range ◽  
Functional Sites ◽  
Wide Range ◽  
And Function ◽  
Intrinsic Reactivity ◽  
Subsequent Target

SummaryNucleophilic amino acids are important in covalent drug development yet underutilized as antimicrobial targets. Over recent years, several chemoproteomic technologies have been developed to mine chemically-accessible residues via their intrinsic reactivity toward electrophilic probes. However, these approaches cannot discern which reactive sites contribute to protein function and should therefore be prioritized for drug discovery. To address this, we have developed a CRISPR-based Oligo Recombineering (CORe) platform to systematically prioritize reactive amino acids according to their contribution to protein function. Our approach directly couples protein sequence and function with biological fitness. Here, we profile the reactivity of >1,000 cysteines on ~700 proteins in the eukaryotic pathogen Toxoplasma gondii and prioritize functional sites using CORe. We competitively compared the fitness effect of 370 codon switches at 74 cysteines and identify functional sites in a diverse range of proteins. In our proof of concept, CORe performed >800 times faster than a standard genetic workflow. Reactive cysteines decorating the ribosome were found to be critical for parasite growth, with subsequent target-based screening validating the apicomplexan translation machinery as a target for covalent ligand development. CORe is system-agnostic, and supports expedient identification, functional prioritization, and rational targeting of reactive sites in a wide range of organisms and diseases.

scholarly journals CoRINs: A tool to compare residue interaction networks from homologous proteins and conformers

2020 ◽  
Author(s):  
Felipe V. da Fonseca ◽  
Romildo O. Souza Júnior ◽  
Marília V. A. de Almeida ◽  
Thiago D. Soares ◽  
Diego A. A. Morais ◽  
...  
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Conformational Changes ◽  
Protein Function ◽  
Protein Structures ◽  
Software Tool ◽  
Interaction Networks ◽  
Homologous Proteins ◽  
Residue Interaction ◽  
And Function

ABSTRACTMotivationA useful approach to evaluate protein structure and quickly visualize crucial physicochemical interactions related to protein function is to construct Residue Interactions Networks (RINs). By using this application of graphs theory, the amino acid residues constitute the nodes, and the edges represent their interactions with other structural elements. Although several tools that construct RINs are available, many of them do not compare RINs from distinct protein structures. This comparison can give valuable insights into the understanding of conformational changes and the effects of amino acid substitutions in protein structure and function. With that in mind, we present CoRINs (Comparator of Residue Interaction Networks), a software tool that extensively compares RINs. The program has an accessible and user-friendly web interface, which summarizes the differences in several network parameters using interactive plots and tables. As a usage example of CoRINs, we compared RINs from conformers of two cancer-associated proteins.AvailabilityThe program is available at https://github.com/LasisUFRN/CoRINs.

High-Resolution Hydroxyl Radical Protein Footprinting: Biophysics Tool for Drug Discovery

2018 ◽  
Vol 47 (1) ◽  
pp. 315-333 ◽  
Author(s):  
Janna Kiselar ◽  
Mark R. Chance
Keyword(s):  
Protein Structure ◽  
High Resolution ◽  
Hydroxyl Radical ◽  
Solvent Accessibility ◽  
Side Chains ◽  
Protein Footprinting ◽  
Hydroxyl Radical Protein Footprinting ◽  
Wide Range ◽  
Hydroxyl Radical Footprinting

Hydroxyl radical footprinting (HRF) of proteins with mass spectrometry (MS) is a widespread approach for assessing protein structure. Hydroxyl radicals react with a wide variety of protein side chains, and the ease with which radicals can be generated (by radiolysis or photolysis) has made the approach popular with many laboratories. As some side chains are less reactive and thus cannot be probed, additional specific and nonspecific labeling reagents have been introduced to extend the approach. At the same time, advances in liquid chromatography and MS approaches permit an examination of the labeling of individual residues, transforming the approach to high resolution. Lastly, advances in understanding of the chemistry of the approach have led to the determination of absolute protein topologies from HRF data. Overall, the technology can provide precise and accurate measures of side-chain solvent accessibility in a wide range of interesting and useful contexts for the study of protein structure and dynamics in both academia and industry.

scholarly journals An Inquiry into Protein Structure and Genetic Disease: Introducing Undergraduates to Bioinformatics in a Large Introductory Course

2005 ◽  
Vol 4 (3) ◽  
pp. 207-220 ◽  
Author(s):  
April E. Bednarski ◽  
Sarah C.R. Elgin ◽  
Himadri B. Pakrasi
Keyword(s):  
Protein Structure ◽  
Genetic Disease ◽  
Protein Function ◽  
Genetic Diseases ◽  
Data Bank ◽  
Mendelian Inheritance ◽  
Single Mutation ◽  
Introductory Course ◽  
And Function ◽  
The Impact

This inquiry-based lab is designed around genetic diseases with a focus on protein structure and function. To allow students to work on their own investigatory projects, 10 projects on 10 different proteins were developed. Students are grouped in sections of 20 and work in pairs on each of the projects. To begin their investigation, students are given a cDNA sequence that translates into a human protein with a single mutation. Each case results in a genetic disease that has been studied and recorded in the Online Mendelian Inheritance in Man (OMIM) database. Students use bioinformatics tools to investigate their proteins and form a hypothesis for the effect of the mutation on protein function. They are also asked to predict the impact of the mutation on human physiology and present their findings in the form of an oral report. Over five laboratory sessions, students use tools on the National Center for Biotechnology Information (NCBI) Web site (BLAST, LocusLink, OMIM, GenBank, and PubMed) as well as ExPasy, Protein Data Bank, ClustalW, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the structure-viewing program DeepView. Assessment results showed that students gained an understanding of the Web-based databases and tools and enjoyed the investigatory nature of the lab.

scholarly journals Iditis: Protein Structure Database

1998 ◽  
Vol 54 (6) ◽  
pp. 1071-1077 ◽  
Author(s):  
Stephen Gardner ◽  
Janet Thornton
Keyword(s):  
User Interface ◽  
Protein Structure ◽  
Experimental Design ◽  
Graphical User Interface ◽  
Molecular Interactions ◽  
Protein Structures ◽  
Structure Database ◽  
Wide Range ◽  
Database Engine

The validation, enrichment and organization of the data stored in PDB files is essential for those data to be used accurately and efficiently for modelling, experimental design and the determination of molecular interactions. TheIditisprotein structure database has been designed to allow the widest possible range of queries to be performed across all available protein structures. TheIditisdatabase is the most comprehensive protein structure resource currently available, and contains over 500 fields of information describing all publicly deposited protein structures. A custom-written database engine and graphical user interface provide a natural and simple environment for the construction of searches for complex sequence- and structure-based motifs. Extensions and specialized interfaces allow the data generated by the database to used in conjunction with a wide range of applications.

INFLUENCE OF PAD GEOMETRY MODIFICATION ON THE PERFORMANCE OF THRUST BEARINGS LUBRICATED WITH MAGNETORHEOLOGICAL FLUID

Tribologia ◽  
2018 ◽  
Vol 278 (2) ◽  
pp. 29-35 ◽  
Author(s):  
Wojciech HORAK ◽  
Marcin SZCZĘCH ◽  
Józef SALWIŃSKI
Keyword(s):  
Sliding Friction ◽  
Experimental Tests ◽  
Magnetic Fluids ◽  
Performance Parameters ◽  
System Operation ◽  
Precise Control ◽  
Thrust Bearings ◽  
Wide Range ◽  
The Magnetic Field

Magnetic fluids belong to the class of controllable materials. The influence of magnetic fields on this type of substance results in a change in its internal structure and an almost immediate change in its rheological properties. The ability to control the rheological characteristics in a very wide range, in combination with the ease of generating and controlling the magnetic field, creates the possibility of using this type of substance in systems with controlled operating parameters. The use of magnetic fluids in bearings may allow the design of some types of bearings to be simplified and enable efficient, fast, and precise control of the system operation, with a much shorter response time and higher stiffness than is the case with conventional sliding friction bearings. The paper presents the results of experimental tests carried out on a laboratory stand designed for thrust bearings lubricated with magnetic fluids. The analyses carried out concerned the determination of how the pad surface modification of the slide bearing, lubricated with magnetorheological fluids, influences the system performance parameters.

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