scholarly journals A Universal Chemical Method for Rational Design of Protein-based Nanoreactors

2021 ◽  
Author(s):  
Mullapudi Mohan Reddy ◽  
Punita Bathla ◽  
Britto S. Sandanaraj
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Chemical Method ◽  
Living Cells ◽  
Protein Labeling ◽  
Self Assembling ◽  
Naturally Occurring ◽  
General Chemical ◽  
Chemical Strategy ◽  
Artificial Protein

AbstractSelf-assembly of a monomeric protease to form a multi-subunit protein complex “proteasome” enables targeted protein degradation in living cells. The naturally occurring proteasomes serve as an inspiration and blueprint for the design of artificial protein-based nanoreactors. Here we disclose a general chemical strategy for the design of proteasome-like nanoreactors. Micelle-assisted protein labeling (MAPLab) technology along with the N-terminal bioconjugation strategy is utilized for the synthesis of a well-defined monodisperse self-assembling semi-synthetic protease. The designer protein is programmed to self-assemble into a proteasome-like nanostructure which preserves the functional properties of native protease.

scholarly journals Rational Design of Self-assembling Artificial Proteins Utilizing a Micelle-Assisted Protein Labeling Technology (MAPLabTech): Testing the Scope

2021 ◽  
Author(s):  
Mullapudi Mohan Reddy ◽  
Pavankumar Janardhan Bhandari ◽  
Britto Sandanaraj
Keyword(s):  
Self Assembly ◽  
Serine Proteases ◽  
Rational Design ◽  
First Generation ◽  
Cysteine Residue ◽  
Protein Labeling ◽  
Site Specific ◽  
Artificial Proteins ◽  
Self Assembling ◽  
Biophysical Studies

Self-assembling artificial proteins (SAPs) have gained enormous interest in recent years due to their applications in different fields. Synthesis of well-defined monodisperse SAPs is accomplished predominantly through genetic methods. However, the last decade witnessed the use of few chemical technologies for that purpose. In particular, micelle-assisted protein labeling technology (MAPLabTech) has made huge progress in this area. The first generation MAPLabTech focused on site-specific labeling of the active-site residue of serine proteases to make SAPs. Further, this methodology was exploited for labeling of N-terminal residue of a globular protein to make functional SAPs. In this study, we describe the synthesis of novel SAPs by developing a chemical method for site-specific labeling of a surface-exposed cysteine residue of globular proteins. In addition, we disclose the synthesis of redox- and pH-sensitive SAPs and their systematic self-assembly and dis-assembly studies using complementary biophysical studies. Altogether these studies further expand the scope of MAPLabTech in different fields such as vaccine design, targeted drug delivery, diagnostic imaging, biomaterials, and tissue engineering.

scholarly journals Self-assembling Peptide Discovery: Overcoming Human Bias With Machine Learning

2021 ◽  
Author(s):  
Rohit Batra ◽  
Troy Loeffler ◽  
Henry Chan ◽  
Srilok Sriniva ◽  
Honggang Cui ◽  
...  
Keyword(s):  
Machine Learning ◽  
Self Assembly ◽  
Search Space ◽  
Sequence Length ◽  
Monte Carlo Tree Search ◽  
Self Assembling ◽  
Naturally Occurring ◽  
Peptide Materials ◽  
Dynamics Simulations ◽  
Better Than

Abstract Peptide materials have a wide array of functions from tissue engineering, surface coatings to catalysis and sensing. This class of biopolymer is composed of a sequence, comprised of 20 naturally occurring amino acids whose arrangement dictate the peptide functionality. While it is highly desirable to tailor the amino acid sequence, a small increase in their sequence length leads to dramatic increase in the possible candidates (e.g., from tripeptide = 20^3 or 8,000 peptides to a pentapeptide = 20^5 or 3.2 M). Traditionally, peptide design is guided by the use of structural propensity tables, hydrophobicity scales, or other desired properties and typically yields <10 peptides per study, barely scraping the surface of the search space. These approaches, driven by human expertise and intuition, are not easily scalable and are riddled with human bias. Here, we introduce a machine learning workflow that combines Monte Carlo tree search and random forest, with molecular dynamics simulations to develop a fully autonomous computational search engine (named, AI-expert) to discover peptide sequences with high potential for self-assembly (as a representative target functionality). We demonstrate the efficacy of the AI-expert to efficiently search large spaces of tripeptides and pentapeptides. Subsequent experiments on the proposed peptide sequences are performed to compare the predictability of the AI-expert with those of human experts. The AI performs on-par or better than human experts and suggests several non-intuitive sequences with high self-assembly propensity, outlining its potential to overcome human bias and accelerate peptide discovery.

The fabrication of self-assembling peptides into nanofiber scaffolds through molecular self-assembly

2004 ◽  
Vol 820 ◽  
Author(s):  
Xiaojun Zhao ◽  
Jessica Dai ◽  
Shuguang Zhang
Keyword(s):  
Cell Cultures ◽  
Self Assembly ◽  
Rational Design ◽  
Biophysical Properties ◽  
Ph Values ◽  
Nanofiber Scaffold ◽  
Self Assembling ◽  
Nanofiber Scaffolds ◽  
D Cell ◽  
Β Sheet

AbstractWe designed and fabricated a class of self-assembling peptides into nanofiber scaffolds. KLDL-12 has been shown to be a permissible nanofiber scaffold for chondrocytes in cartilage 3-D cell cultures. However, the biochemical, structural, and biophysical properties of KLDL- 12 remain unclear. We show that KLDL-12 peptides form stable β-sheet structures at different pH values and that KLDL-12 and RIDI-12 self-assemble into nanofibers. The nanofiber length, though, is sensitive to pH changes. These results not only suggest the importance of electrostatic attraction or repulsion affecting the fiber lengths but also provide us with useful information for rational design and fabrication of peptide scaffolds.

scholarly journals Responsive self-assembly of tectoRNAs with loop–receptor interactions from the tetrahydrofolate (THF) riboswitch

2019 ◽  
Vol 47 (12) ◽  
pp. 6439-6451 ◽  
Author(s):  
Charles Mitchell ◽  
Julio A Polanco ◽  
Laura DeWald ◽  
Dustin Kress ◽  
Luc Jaeger ◽  
...  
Keyword(s):  
Self Assembly ◽  
Structural Features ◽  
Receptor Interaction ◽  
Structural Elements ◽  
Rna Nanotechnology ◽  
Self Assembling ◽  
Naturally Occurring ◽  
Receptor Interactions ◽  
Overall Performance ◽  
High Degree

Abstract Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific structural modules (or motifs) can be mixed and matched to create new molecular architectures. The modular nature of RNA also affords researchers the ability to characterize individual structural elements in controlled synthetic contexts in order to gain new and critical insights into their particular structural features and overall performance. Here, we characterized the binding affinity of a unique loop–receptor interaction found in the tetrahydrofolate (THF) riboswitch using rationally designed self-assembling tectoRNAs. Our work suggests that the THF loop–receptor interaction has been fine-tuned for its particular role as a riboswitch component. We also demonstrate that the thermodynamic stability of this interaction can be modulated by the presence of folinic acid, which induces a local structural change at the level of the loop–receptor. This corroborates the existence of a THF binding site within this tertiary module and paves the way for its potential use as a THF responsive module for RNA nanotechnology and synthetic biology.

Designer functionalised self-assembling peptide nanofibre scaffolds for cartilage tissue engineering

2014 ◽  
Vol 16 ◽  
Author(s):  
Bin He ◽  
Xiao Yuan ◽  
Aiguo Zhou ◽  
Hua Zhang ◽  
Dianming Jiang
Keyword(s):  
Tissue Engineering ◽  
Self Assembly ◽  
Rational Design ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Regenerative Capacity ◽  
Self Assembling ◽  
Important Approach ◽  
Biomaterial Scaffolds

Owing to the limited regenerative capacity of cartilage tissue, cartilage repair remains a challenge in clinical treatment. Tissue engineering has emerged as a promising and important approach to repair cartilage defects. It is well known that material scaffolds are regarded as a fundamental element of tissue engineering. Novel biomaterial scaffolds formed by self-assembling peptides consist of nanofibre networks highly resembling natural extracellular matrices, and their fabrication is based on the principle of molecular self-assembly. Indeed, peptide nanofibre scaffolds have obtained much progress in repairing various damaged tissues (e.g. cartilage, bone, nerve, heart and blood vessel). This review outlines the rational design of peptide nanofibre scaffolds and their potential in cartilage tissue engineering.

Rational design of patchy colloidsvialandscape engineering

2018 ◽  
Vol 3 (1) ◽  
pp. 49-65 ◽  
Author(s):  
Andrew W. Long ◽  
Andrew L. Ferguson
Keyword(s):  
Free Energy ◽  
Self Assembly ◽  
Rational Design ◽  
Energy Landscape ◽  
Building Blocks ◽  
Inverse Design ◽  
Free Energy Landscape ◽  
New Approach ◽  
Self Assembling

A new approach for inverse design of self-assembling building blocks by rational sculpting of the underlying self-assembly free energy landscape.

scholarly journals Carbocycle-Based Organogelators: Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties

Gels ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 54
Author(s):  
Rosa M. Ortuño
Keyword(s):  
Smart Materials ◽  
Self Assembly ◽  
Rational Design ◽  
Structural Features ◽  
Stimuli Responsive ◽  
Polycyclic Compounds ◽  
Relative Configuration ◽  
Responsive Materials ◽  
Self Assembling ◽  
Donor Acceptor

The rational design and engineer of organogel-based smart materials and stimuli-responsive materials with tuned properties requires the control of the non-covalent forces driving the hierarchical self-assembly. Chirality, as well as cis/trans relative configuration, also plays a crucial role promoting the morphology and characteristics of the aggregates. Cycloalkane derivatives can provide chiral chemical platforms allowing the incorporation of functional groups and hydrophobic structural units able for a convenient molecular stacking leading to gels. Restriction of the conformational freedom imposed by the ring strain is also a contributing issue that can be modulated by the inclusion of flexible segments. In addition, donor/acceptor moieties can also be incorporated favoring the interactions with light or with charged species. This review offers a perspective on the abilities and properties of carbocycle-based organogelators starting from simple cycloalkane derivatives, which were the key to establish the basis for an effective self-assembling, to sophisticated polycyclic compounds with manifold properties and applications.

The fabrication of self-assembling peptides into nanofiber scaffolds through molecular self-assembly

2004 ◽  
Vol 823 ◽  
Author(s):  
Xiaojun Zhao ◽  
Jessica Dai ◽  
Shuguang Zhang
Keyword(s):  
Cell Cultures ◽  
Self Assembly ◽  
Rational Design ◽  
Biophysical Properties ◽  
Ph Values ◽  
Nanofiber Scaffold ◽  
Self Assembling ◽  
Nanofiber Scaffolds ◽  
D Cell ◽  
Β Sheet

AbstractWe designed and fabricated a class of self-assembling peptides into nanofiber scaffolds. KLDL-12 has been shown to be a permissible nanofiber scaffold for chondrocytes in cartilage 3-D cell cultures. However, the biochemical, structural, and biophysical properties of KLDL-12 remain unclear. We show that KLDL-12 peptides form stable β-sheet structures at different pH values and that KLDL-12 and RIDI-12 self-assemble into nanofibers. The nanofiber length, though, is sensitive to pH changes. These results not only suggest the importance of electrostatic attraction or repulsion affecting the fiber lengths but also provide us with useful information for rational design and fabrication of peptide scaffolds.

Factors Affecting Molecular Self-Assembly and Its Mechanism

2012 ◽  
Vol 9 (1) ◽  
pp. 43 ◽  
Author(s):  
Hueyling Tan
Keyword(s):  
Self Assembly ◽  
Building Blocks ◽  
Molecular Engineering ◽  
Molecular Structures ◽  
Polymer Science ◽  
New Approach ◽  
Factors Affecting ◽  
Dna Structures ◽  
Self Assembling ◽  
Wide Range

Molecular self-assembly is ubiquitous in nature and has emerged as a new approach to produce new materials in chemistry, engineering, nanotechnology, polymer science and materials. Molecular self-assembly has been attracting increasing interest from the scientific community in recent years due to its importance in understanding biology and a variety of diseases at the molecular level. In the last few years, considerable advances have been made in the use ofpeptides as building blocks to produce biological materials for wide range of applications, including fabricating novel supra-molecular structures and scaffolding for tissue repair. The study ofbiological self-assembly systems represents a significant advancement in molecular engineering and is a rapidly growing scientific and engineering field that crosses the boundaries ofexisting disciplines. Many self-assembling systems are rangefrom bi- andtri-block copolymers to DNA structures as well as simple and complex proteins andpeptides. The ultimate goal is to harness molecular self-assembly such that design andcontrol ofbottom-up processes is achieved thereby enabling exploitation of structures developed at the meso- and macro-scopic scale for the purposes oflife and non-life science applications. Such aspirations can be achievedthrough understanding thefundamental principles behind the selforganisation and self-synthesis processes exhibited by biological systems.

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