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Special Issue "Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: 28 February 2021.

Special Issue Editors

Prof. Dr. Ayae Sugawara-Narutaki
Website
Guest Editor
Department of Materials Chemistry, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
Special Issues and Collections in MDPI journals
Dr. Yukiko Kamiya
Website
Guest Editor
Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Nature has evolved sequence-controlled polymers like DNA and proteins over its long history. The recent rapid progress of synthetic chemistry, DNA recombinant technology, and computational science, as well as the elucidation of molecular mechanisms in biological processes, drive us to design ingenious polymers that are inspired by naturally occurring polymers but surpass them in specialized functions. The term “designer biopolymers” refers to polymers consisting of biological building units such as nucleotides, amino acids, and monosaccharides in a sequence-controlled manner. They may contain non-canonical nucleotides/amino acids/monosaccharides, or they may be conjugated to synthetic polymers to acquire specific functions in vitro and in vivo.

This Special Issue particularly focuses on the self-assembling aspect of designer biopolymers. Self-assembly is one common feature in biopolymers to realize their dynamic biological activities, and is strictly controlled by the sequence of biopolymers. In a broad sense, the self-assembly of biopolymers includes double-helix formation of DNA, protein folding, and higher-order protein assembly (e.g., viral capsids). Designer biopolymers are now going beyond what nature evolved: researchers have generated DNA origami, protein cages, peptide nanofibers, and gels. The aim of this Special Issue is to assemble the latest interdisciplinary work on self-assembling designer biopolymers to exchange ideas and encourage new lines of research.

Prof. Dr. Ayae Sugawara-Narutaki
Prof. Dr. Yukiko Kamiya
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • de novo protein design
  • Artificial nucleic acids/peptides
  • Self-assembling peptides/proteins
  • DNA nanotechnology
  • Nanofibers and gels of nucleic acids/proteins/peptides
  • Stimuli-responsive designer biopolymers
  • Tissue engineering scaffolding

Related Special Issue

Published Papers (8 papers)

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Research

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Open AccessArticle
Investigation of Strand-Selective Interaction of SNA-Modified siRNA with AGO2-MID
Int. J. Mol. Sci. 2020, 21(15), 5218; https://doi.org/10.3390/ijms21155218 - 23 Jul 2020
Cited by 1
Abstract
Small interfering RNA (siRNA) has been recognized as a powerful gene-silencing tool. For therapeutic application, chemical modification is often required to improve the properties of siRNA, including its nuclease resistance, activity, off-target effects, and tissue distribution. Careful siRNA guide strand selection in the [...] Read more.
Small interfering RNA (siRNA) has been recognized as a powerful gene-silencing tool. For therapeutic application, chemical modification is often required to improve the properties of siRNA, including its nuclease resistance, activity, off-target effects, and tissue distribution. Careful siRNA guide strand selection in the RNA-induced silencing complex (RISC) is important to increase the RNA interference (RNAi) activity as well as to reduce off-target effects. The passenger strand-mediated off-target activity was previously reduced and on-target activity was enhanced by substitution with acyclic artificial nucleic acid, namely serinol nucleic acid (SNA). In the present study, the reduction of off-target activity caused by the passenger strand was investigated by modifying siRNAs with SNA. The interactions of SNA-substituted mononucleotides, dinucleotides, and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)-labeled double-stranded RNA (dsRNA) with the MID domain of the Argonaute 2 (AGO2) protein, which plays a pivotal role in strand selection by accommodation of the 5’-terminus of siRNA, were comprehensively analyzed. The obtained nuclear magnetic resonance (NMR) data revealed that AGO2-MID selectively bound to the guide strand of siRNA due to the inhibitory effect of the SNA backbone located at the 5’ end of the passenger strand. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessArticle
On the Catalytic Activity of the Engineered Coiled-Coil Heptamer Mimicking the Hydrolase Enzymes: Insights from a Computational Study
Int. J. Mol. Sci. 2020, 21(12), 4551; https://doi.org/10.3390/ijms21124551 - 26 Jun 2020
Abstract
Recently major advances were gained on the designed proteins aimed to generate biomolecular mimics of proteases. Although such enzyme-like catalysts must still suffer refinements for improving the catalytic activity, at the moment, they represent a good example of artificial enzymes to be tested [...] Read more.
Recently major advances were gained on the designed proteins aimed to generate biomolecular mimics of proteases. Although such enzyme-like catalysts must still suffer refinements for improving the catalytic activity, at the moment, they represent a good example of artificial enzymes to be tested in different fields. Herein, a de novo designed homo-heptameric peptide assembly (CC-Hept) where the esterase activity towards p-nitro-phenylacetate was obtained for introduction of the catalytic triad (Cys-His-Glu) into the hydrophobic matrix, is the object of the present combined molecular dynamics and quantum mechanics/molecular mechanics investigation. Constant pH Molecular Dynamics simulations on the apoform of CC-Hept suggested that the Cys residues are present in the protonated form. Molecular dynamics (MD) simulations of the enzyme–substrate complex evidenced the attitude of the enzyme-like system to retain water molecules, necessary in the hydrolytic reaction, in correspondence of the active site, represented by the Cys-His-Glu triad on each of the seven chains, without significant structural perturbations. A detailed reaction mechanism of esterase activity of CC-Hept-Cys-His-Glu was investigated on the basis of the quantum mechanics/molecular mechanics calculations employing a large quantum mechanical (QM) region of the active site. The proposed mechanism is consistent with available esterases kinetics and structural data. The roles of the active site residues were also evaluated. The deacylation phase emerged as the rate-determining step, in agreement with esterase activity of other natural proteases. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessCommunication
Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids
Int. J. Mol. Sci. 2020, 21(6), 2001; https://doi.org/10.3390/ijms21062001 - 15 Mar 2020
Abstract
The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues [...] Read more.
The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessArticle
Chemically Crosslinked Bispecific Antibodies for Cancer Therapy: Breaking from the Structural Restrictions of the Genetic Fusion Approach
Int. J. Mol. Sci. 2020, 21(3), 711; https://doi.org/10.3390/ijms21030711 - 21 Jan 2020
Abstract
Antibodies are composed of structurally and functionally independent domains that can be used as building blocks to construct different types of chimeric protein-format molecules. However, the generally used genetic fusion and chemical approaches restrict the types of structures that can be formed and [...] Read more.
Antibodies are composed of structurally and functionally independent domains that can be used as building blocks to construct different types of chimeric protein-format molecules. However, the generally used genetic fusion and chemical approaches restrict the types of structures that can be formed and do not give an ideal degree of homogeneity. In this study, we combined mutation techniques with chemical conjugation to construct a variety of homogeneous bivalent and bispecific antibodies. First, building modules without lysine residues—which can be chemical conjugation sites—were generated by means of genetic mutation. Specific mutated residues in the lysine-free modules were then re-mutated to lysine residues. Chemical conjugation at the recovered lysine sites enabled the construction of homogeneous bivalent and bispecific antibodies from block modules that could not have been so arranged by genetic fusion approaches. Molecular evolution and bioinformatics techniques assisted in finding viable alternatives to the lysine residues that did not deactivate the block modules. Multiple candidates for re-mutation positions offer a wide variety of possible steric arrangements of block modules, and appropriate linkages between block modules can generate highly bioactive bispecific antibodies. Here, we propose the effectiveness of the lysine-free block module design for site-specific chemical conjugation to form a variety of types of homogeneous chimeric protein-format molecule with a finely tuned structure and function. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessArticle
On-Membrane Dynamic Interplay between Anti-GM1 IgG Antibodies and Complement Component C1q
Int. J. Mol. Sci. 2020, 21(1), 147; https://doi.org/10.3390/ijms21010147 - 24 Dec 2019
Cited by 1
Abstract
Guillain–Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness, is often preceded by Campylobacter jejuni infection. Molecular mimicry exists between the bacterial lipo-oligosaccharide and human ganglioside. Such C. jejuni infection induces production of immunoglobulin G1 (IgG1) autoantibodies against GM1 and causes complement-mediated [...] Read more.
Guillain–Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness, is often preceded by Campylobacter jejuni infection. Molecular mimicry exists between the bacterial lipo-oligosaccharide and human ganglioside. Such C. jejuni infection induces production of immunoglobulin G1 (IgG1) autoantibodies against GM1 and causes complement-mediated motor nerve injury. For elucidating the molecular mechanisms linking autoantigen recognition and complement activation, we characterized the dynamic interactions of anti-GM1 IgG autoantibodies on ganglioside-incorporated membranes. Using high-speed atomic force microscopy, we found that the IgG molecules assemble into a hexameric ring structure on the membranes depending on their specific interactions with GM1. Complement component C1q was specifically recruited onto these IgG rings. The ring formation was inhibited by an IgG-binding domain of staphylococcal protein A bound at the cleft between the CH2 and CH3 domains. These data indicate that the IgG assembly is mediated through Fc–Fc interactions, which are promoted under on-membrane conditions due to restricted translational diffusion of IgG molecules. Reduction and alkylation of the hinge disulfide impaired IgG ring formation, presumably because of an increase in conformational entropic penalty. Our findings provide mechanistic insights into the molecular processes involved in Guillain–Barré syndrome and, more generally, into antigen-dependent interplay between antibodies and complement components on membranes. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessArticle
Rheology of Dispersions of High-Aspect-Ratio Nanofibers Assembled from Elastin-Like Double-Hydrophobic Polypeptides
Int. J. Mol. Sci. 2019, 20(24), 6262; https://doi.org/10.3390/ijms20246262 - 12 Dec 2019
Abstract
Elastin-like polypeptides (ELPs) are promising candidates for fabricating tissue-engineering scaffolds that mimic the extracellular environment of elastic tissues. We have developed a “double-hydrophobic” block ELP, GPG, inspired by non-uniform distribution of two different hydrophobic domains in natural elastin. GPG has a block [...] Read more.
Elastin-like polypeptides (ELPs) are promising candidates for fabricating tissue-engineering scaffolds that mimic the extracellular environment of elastic tissues. We have developed a “double-hydrophobic” block ELP, GPG, inspired by non-uniform distribution of two different hydrophobic domains in natural elastin. GPG has a block sequence of (VGGVG)5-(VPGXG)25-(VGGVG)5 that self-assembles to form nanofibers in water. Functional derivatives of GPG with appended amino acid motifs can also form nanofibers, a display of the block sequence’s robust self-assembling properties. However, how the block length affects fiber formation has never been clarified. This study focuses on the synthesis and characterization of a novel ELP, GPPG, in which the central sequence (VPGVG)25 is repeated twice by a short linker sequence. The self-assembly behavior and the resultant nanostructures of GPG and GPPG were when compared through circular dichroism spectroscopy, atomic force microscopy, and transmission electron microscopy. Dynamic rheology measurements revealed that the nanofiber dispersions of both GPG and GPPG at an extremely low concentration (0.034 wt%) exhibited solid-like behavior with storage modulus G′ > loss modulus G” over wide range of angular frequencies, which was most probably due to the high aspect ratio of the nanofibers that leads to the flocculation of nanofibers in the dispersion. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Open AccessArticle
Hot Spots and Their Contribution to the Self-Assembly of the Viral Capsid: In Silico Prediction and Analysis
Int. J. Mol. Sci. 2019, 20(23), 5966; https://doi.org/10.3390/ijms20235966 - 27 Nov 2019
Cited by 1
Abstract
The viral capsid is a macromolecular complex formed by a defined number of self-assembled proteins, which, in many cases, are biopolymers with an identical amino acid sequence. Specific protein–protein interactions (PPI) drive the capsid self-assembly process, leading to several distinct protein interfaces. Following [...] Read more.
The viral capsid is a macromolecular complex formed by a defined number of self-assembled proteins, which, in many cases, are biopolymers with an identical amino acid sequence. Specific protein–protein interactions (PPI) drive the capsid self-assembly process, leading to several distinct protein interfaces. Following the PPI hot spot hypothesis, we present a conservation-based methodology to identify those interface residues hypothesized to be crucial elements on the self-assembly and thermodynamic stability of the capsid. We validate the predictions through a rigorous physical framework which integrates molecular dynamics simulations and free energy calculations by Umbrella sampling and the potential of mean force using an all-atom molecular representation of the capsid proteins of an icosahedral virus in an explicit solvent. Our results show that a single mutation in any of the structure-conserved hot spots significantly perturbs the quaternary protein–protein interaction, decreasing the absolute value of the binding free energy, without altering the protein’s secondary nor tertiary structure. Our conservation-based hot spot prediction methodology can lead to strategies to rationally modulate the capsid’s thermodynamic properties. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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Review

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Open AccessReview
Coiled-Coils: The Molecular Zippers that Self-Assemble Protein Nanostructures
Int. J. Mol. Sci. 2020, 21(10), 3584; https://doi.org/10.3390/ijms21103584 - 19 May 2020
Cited by 1
Abstract
Coiled-coils, the bundles of intertwined helical protein motifs, have drawn much attention as versatile molecular toolkits. Because of programmable interaction specificity and affinity as well as well-established sequence-to-structure relationships, coiled-coils have been used as subunits that self-assemble various molecular complexes in a range [...] Read more.
Coiled-coils, the bundles of intertwined helical protein motifs, have drawn much attention as versatile molecular toolkits. Because of programmable interaction specificity and affinity as well as well-established sequence-to-structure relationships, coiled-coils have been used as subunits that self-assemble various molecular complexes in a range of fields. In this review, I describe recent advances in the field of protein nanotechnology, with a focus on programming assembly of protein nanostructures using coiled-coil modules. Modular design approaches to converting the helical motifs into self-assembling building blocks are described, followed by a discussion on the molecular basis and principles underlying the modular designs. This review also provides a summary of recently developed nanostructures with a variety of structural features, which are in categories of unbounded nanostructures, discrete nanoparticles, and well-defined origami nanostructures. Challenges existing in current design strategies, as well as desired improvements for controls over material properties and functionalities for applications, are also provided. Full article
(This article belongs to the Special Issue Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids 2020)
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