Proton translocation enables important processes in nature and man-made technologies. However, controlling proton conduction and fabrication of devices exploiting biomaterials remains a challenge. Even more difficult is the design of protein-based bulk materials without any functional starting scaffold for further optimization. Here, we show the rational design of proton-conducting, protein materials exceeding reported proteinaceous systems. The carboxylic acid-rich structures were evolved step by step by exploring various sequences from intrinsically disordered coils over supercharged nanobarrels to hierarchically spider β sheet containing protein-supercharged polypeptide chimeras. The latter material is characterized by interconnected β sheet nanodomains decorated on their surface by carboxylic acid groups, forming self-supportive membranes and allowing for proton conduction in the hydrated state. The membranes showed an extraordinary proton conductivity of 18.5 ± 5 mS/cm at RH = 90%, one magnitude higher than other protein devices. This design paradigm offers great potential for bioprotonic device fabrication interfacing artificial and biological systems.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439445 | PMC |
| http://dx.doi.org/10.1126/sciadv.abc0810 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Computational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFAdvancing the Mechanosensitivity of Atropisomeric Diarylethene Mechanophores through a Lever-Arm Effect.
J Am Chem Soc
January 2025
Department of Chemistry, BioInspired Institute, Syracuse University, Syracuse, New York 13244, United States.
Understanding structure-mechanical activity relationships (SMARs) in polymer mechanochemistry is essential for the rational design of mechanophores with desired properties, yet SMARs in noncovalent mechanical transformations remain relatively underexplored. In this study, we designed a subset of diarylethene mechanophores based on a lever-arm hypothesis and systematically investigated their mechanical activity toward a noncovalent-yet-chemical conversion of atropisomer stereochemistry. Results from Density functional theory (DFT) calculations, single-molecule force spectroscopy (SMFS) measurements, and ultrasonication experiments collectively support the lever-arm hypothesis and confirm the exceptional sensitivity of chemo-mechanical coupling in these atropisomers.
View Article and Find Full Text PDFPredicting the polyspecificity of aminoacyl-tRNA synthetase for non-canonical amino acids using molecular dynamics simulation and MM/PBSA.
PLoS One
January 2025
Department of Biotechnology and Bioengineering, Chonnam National University, Gwangju, Republic of Korea.
With the advancement of genetic code expansion, the field is progressing towards incorporating multiple non-canonical amino acids (ncAAs). The specificity of aminoacyl-tRNA synthetases (aaRSs) towards ncAAs is a critical factor, as engineered aaRSs frequently show polyspecificity, complicating the precise incorporation of multiple ncAAs. To address this challenge, predicting binding affinity can be beneficial.
View Article and Find Full Text PDFEvaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.
Chem Biol Drug Des
January 2025
Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.
View Article and Find Full Text PDFRational design of redox active metal organic frameworks for mediated electron transfer of enzymes.
Mater Horiz
January 2025
Department of Material Sciences, Institute of Pure and Applied Sciences, University of Tsukuba, 1-1-1, Tennodai, Ibaraki 305-5358, Japan.
The efficient immobilization of redox mediators remains a major challenge in the design of mediated enzyme electrode platforms. In addition to stability, the ability of the redox-active material to mediate electron transfer from the active-site buried enzymes, such as flavin adenine dinucleotide-dependent glucose dehydrogenase (FADGDH) and lactate oxidase (LOx), is also crucial. Conventional immobilization techniques can be synthetically challenging, and immobilized mediators often exhibit limited durability, particularly in continuous operation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!