Protein Surface Printer for Exploring Protein Domains

Yang, Li; Qiao, Botao; Cruz, Mónica Olvera de la

doi:10.1021/acs.jcim.0c00582

Cited by 3 publications

(2 citation statements)

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“…Indeed, to achieve protein coassembly with random copolymers into various structures, from hydrogels to single-protein encapsulation, the monomer chemical composition for specific protein surface domains is required, as well as understanding the cooperative interactions between the different chemical groups. Sophisticated computational algorithms have shown a great ability to quickly classify the protein surface domains; − however, a synergistic and chemically precise analysis on the interactions among enzymes and polymers in an aqueous solution is still lacking, which is strongly suggested to address a more rational design of direct enzyme–random copolymer self-assembly.…”

Section: Introductionmentioning

confidence: 99%

A Modeling-Based Design to Engineering Protein Hydrogels with Random Copolymers

et al. 2021

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Protein enzymes have shown great potential in numerous technological applications. However, the design of supporting materials is needed to preserve protein functionality outside their native environment. Direct enzyme−polymer selfassembly offers a promising alternative to immobilize proteins in an aqueous solution, achieving higher control of their stability and enzymatic activity in industrial applications. Herein, we propose a modeling-based design to engineering hydrogels of cytochrome P450 and of PETase with styrene/2-vinylpyridine (2VP) random copolymers. By tuning the copolymer fraction of polar groups and of charged groups via quaternization of 2VP for coassembly with cytochrome P450 and via sulfonation of styrene for coassembly with PETase, we provide quantitative guidelines to select either a protein−polymer hydrogel structure or a single-protein encapsulation. The results highlight that, regardless of the protein surface domains, the presence of polar interactions and hydration effects promote the formation of a more elongated enzyme−polymer complex, suggesting a membrane-like coassembly. On the other hand, the effectiveness of a single-protein encapsulation is reached by decreasing the fraction of polar groups and by increasing the charge fraction up to 15%. Our computational analysis demonstrates that the enzyme−polymer assemblies are first promoted by the hydrophobic interactions which lead the protein nonpolar residues to achieve the maximum coverage and to play the role of the most robust contact points. The mechanisms of coassembly are unveiled in the light of both protein and polymer physical-chemistry, providing bioconjugate phase diagrams for the optimal material design.

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Section: Introductionmentioning

confidence: 99%

A Modeling-Based Design to Engineering Protein Hydrogels with Random Copolymers

et al. 2021

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“…The binding energy between trypsin molecules and the NP was calculated with the gmx energy tool. The compositions of the trypsin binding domains were analyzed with our recently developed program Protein Surface Printer 47 . The results indicated there were no preference for binding orientations of trypsin.…”

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Bioactive hard protein coronas on poly(propylene sulfone) surfaces enable mast cell nanotherapy

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Rische²,

Li³

et al. 2022

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Contact between nanomaterials and biomolecules such as serum proteins leads to “soft” or “hard” corona formation via dynamic or irreversible adsorption, respectively. While soft coronas of antibodies can temporarily retain the ability for immunological recognition, preserving protein function within hard coronas has remained an elusive goal due to the unfolding of protein at the nano-bio interface. Here, we show that poly(propylene sulfone) nanoparticles efficiently and stably adsorb proteins, unexpectedly forming bioactive hard coronas using a facile methodology. This process is permitted by site-specific hydrophobic-hydrophobic interactions between nanoparticle surfaces and proteins, allowing stable simultaneous pre-adsorption of multiple proteins such as enzymes and antibodies. For therapeutic validation, a nanotherapy for enhanced antibody-based targeting of mast cells and inhibition of anaphylaxis was demonstrated in a humanized mouse model. Protein immobilization on the poly(propylene sulfone) surface therefore provides a simple and rapid platform for the design, fabrication, and optimization of bioactive and targeted nanomedicines.

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