scholarly journals Self-assembly–based posttranslational protein oscillators

2020 ◽  
Vol 6 (51) ◽  
pp. eabc1939
Author(s):  
Ofer Kimchi ◽  
Carl P. Goodrich ◽  
Alexis Courbet ◽  
Agnese I. Curatolo ◽  
Nicholas B. Woodall ◽  
...  
Keyword(s):  
Protein Design ◽  
Dynamic Systems ◽  
Self Assembly ◽  
Rational Design ◽  
Protein Species ◽  
Gene Circuits ◽  
Reversible Binding ◽  
Restricted Parameter Space ◽  
Recent Advances ◽  
Dynamic Phenomena

Recent advances in synthetic posttranslational protein circuits are substantially impacting the landscape of cellular engineering and offer several advantages compared to traditional gene circuits. However, engineering dynamic phenomena such as oscillations in protein-level circuits remains an outstanding challenge. Few examples of biological posttranslational oscillators are known, necessitating theoretical progress to determine realizable oscillators. We construct mathematical models for two posttranslational oscillators, using few components that interact only through reversible binding and phosphorylation/dephosphorylation reactions. Our designed oscillators rely on the self-assembly of two protein species into multimeric functional enzymes that respectively inhibit and enhance this self-assembly. We limit our analysis to within experimental constraints, finding (i) significant portions of the restricted parameter space yielding oscillations and (ii) that oscillation periods can be tuned by several orders of magnitude using recent advances in computational protein design. Our work paves the way for the rational design and realization of protein-based dynamic systems.

scholarly journals Self-assembly based post-translational protein oscillators

2020 ◽  
Author(s):  
Ofer Kimchi ◽  
Carl P. Goodrich ◽  
Alexis Courbet ◽  
Agnese I. Curatolo ◽  
Nicholas B. Woodall ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Self Assembly ◽  
Reversible Binding ◽  
Number Of Components ◽  
Recent Advances ◽  
Dynamic Phenomena

Recent advances in synthetic post-translational protein circuits are significantly impacting the landscape of biomimicry engineering. However, designing sustained dynamic phenomena in these circuits remains an outstanding challenge. Inspired by the KaiABC system regulating the circadian clock in cyanobacteria, we develop two experimentally realizable post-translational oscillators. The oscillators rely on a small number of components interacting only through reversible binding and phosphorylation/dephosphorylation reactions.

scholarly journals Recent advances in short peptide self-assembly: from rational design to novel applications

2020 ◽  
Vol 45 ◽  
pp. 1-13 ◽  
Author(s):  
Xuzhi Hu ◽  
Mingrui Liao ◽  
Haoning Gong ◽  
Lin Zhang ◽  
Henry Cox ◽  
...  
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Short Peptide ◽  
Recent Advances ◽  
Novel Applications

Recent Advances on Paclitaxel-based Self-Delivery Nanomedicine for Cancer Therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Mengjiao Zhou ◽  
Shupeng Han ◽  
Feifei An
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Rational Design ◽  
Water Solubility ◽  
Drug Loading ◽  
The Self ◽  
Drug Molecules ◽  
Recent Advances ◽  
Effective Combination

: Paclitaxel (PTX) is the first natural plant-derived chemotherapeutic drug approved by the Food and Drug Administration. However, the clinical applications of PTX are limited by some drawbacks, such as poor water solubility, rapid blood clearance, nonspecific distribution, and adverse side effects. Nanocarriers have made important contributions for drug delivery and cancer therapy in recent years. However, low drug loading capacity, nanocarrier excipients-induced toxicity or immunogenicity, and complicated synthesis technologies pose a challenge for the clinical application of nanocarriers. To address these issues, the self-delivery nanomedicine (SDNs), in which pure drug molecules directly self-assemble into nanomedicine, have been developed for drug delivery and enhancing antitumor efficacy. In this review, we comprehensively summarize the recent advances on PTX-based SDNs for cancer therapy. First, the self-assembly strategies to develop pure PTX nanodrugs are discussed. Then, the emerging strategies of co-assembly PTX and other therapeutic agents for effective combination therapy are presented, composing of combination chemotherapy, chemo-photothermal therapy, chemophotodynamic therapy, chemo-immunotherapy, and chemo-gene therapy. Finally, the limitations and future outlook of SDNs are discussed. The rational design of these unique nanoplatforms may make a new direction to develop highly efficient drug delivery systems for cancer therapy.

A Dynamic Systems Approach to Personality

2001 ◽  
Vol 6 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Lawrence A. Pervin
Keyword(s):  
Dynamic Systems ◽  
Systems Approach ◽  
Biological Processes ◽  
Recent Advances ◽  
Dynamic View ◽  
The Future ◽  
History Of

David Magnusson has been the most articulate spokesperson for a holistic, systems approach to personality. This paper considers three concepts relevant to a dynamic systems approach to personality: dynamics, systems, and levels. Some of the history of a dynamic view is traced, leading to an emphasis on the need for stressing the interplay among goals. Concepts such as multidetermination, equipotentiality, and equifinality are shown to be important aspects of a systems approach. Finally, attention is drawn to the question of levels of description, analysis, and explanation in a theory of personality. The importance of the issue is emphasized in relation to recent advances in our understanding of biological processes. Integrating such advances into a theory of personality while avoiding the danger of reductionism is a challenge for the future.

Recent advances in the rational design of 2D MXenes in energy conversion and storage systems

2021 ◽  
Author(s):  
Nayab Sheikh ◽  
Muhammad Bilal Tahir ◽  
Nisar Fatima ◽  
Muhammad Sagir ◽  
Muhammad Pervaiz ◽  
...  
Keyword(s):  
Energy Conversion ◽  
Rational Design ◽  
Storage Systems ◽  
Recent Advances ◽  
Energy Conversion And Storage ◽  
And Storage

scholarly journals Recent advances in de novo protein design: principles, methods, and applications

2021 ◽  
pp. 100558
Author(s):  
Xingjie Pan ◽  
Tanja Kortemme
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Design Principles ◽  
Recent Advances ◽  
De Novo Protein Design

scholarly journals Hydroxylated phosphines as ligands for chalcogenide clusters: self assembly, transformations and stabilization

2017 ◽  
Vol 89 (3) ◽  
pp. 379-392 ◽  
Author(s):  
Maxim N. Sokolov ◽  
Alexander V. Anyushin ◽  
Rita Hernandez-Molina ◽  
Rosa Llusar ◽  
Manuel G. Basallote
Keyword(s):  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Self Assembly ◽  
Structure Elucidation ◽  
Alkyl Chain ◽  
Chalcogenide Clusters ◽  
Recent Advances

AbstractThis contribution is a documentation of recent advances in the chemistry of chalcogenide polynuclear transition metal complexes coordinated with mono- and di-phosphines functionalized with hydroxo groups. A survey of complexes containing tris(hydroxymethyl)phosphine (THP) is presented. The influence of the alkyl chain in bidentate phosphines, bearing the P–(CH2)x–OH arms, is also analyzed. Finally, isolation and structure elucidation of the complexes with HP(OH)2, P(OH)3, As(OH)3, PhP(OH)2, stabilized by coordination to Ni(0) and Pd(0) centers embedded into chalcogenide clusters, is discussed.

Examining the structure of the mature amyloid fibril

2002 ◽  
Vol 30 (4) ◽  
pp. 521-525 ◽  
Author(s):  
O. S. Makin ◽  
L. C. Serpell
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Amyloid Fibrils ◽  
Structural Information ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cryo Electron Microscopy ◽  
Fibre Diffraction ◽  
Complementary Techniques ◽  
Mature Fibril

The pathogenesis of the group of diseases known collectively as the amyloidoses is characterized by the deposition of insoluble amyloid fibrils. These are straight, unbranching structures about 70–120 å (1 å = 0.1 nm) in diameter and of indeterminate length formed by the self-assembly of a diverse group of normally soluble proteins. Knowledge of the structure of these fibrils is necessary for the understanding of their abnormal assembly and deposition, possibly leading to the rational design of therapeutic agents for their prevention or disaggregation. Structural elucidation is impeded by fibril insolubility and inability to crystallize, thus preventing the use of X-ray crystallography and solution NMR. CD, Fourier-transform infrared spectroscopy and light scattering have been used in the study of the mechanism of fibril formation. This review concentrates on the structural information about the final, mature fibril and in particular the complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray fibre diffraction.

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