Designed for life: biocompatible de novo designed proteins and components

A principal goal of synthetic biology is the de novo design or redesign of biomolecular components. In addition to revealing fundamentally important information regarding natural biomolecular engineering and biochemistry, functional building blocks will ultimately be provided for applications including the manufacture of valuable products and therapeutics. To fully realize this ambitious goal, the designed components must be biocompatible, working in concert with natural biochemical processes and pathways, while not adversely affecting cellular function. For example, de novo protein design has provided us with a wide repertoire of structures and functions, including those that can be assembled and function in vivo . Here we discuss such biocompatible designs, as well as others that have the potential to become biocompatible, including non-protein molecules, and routes to achieving full biological integration.

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Protein designer David Baker: I like doing things that seem like magic

National Science Review ◽

10.1093/nsr/nwaa071 ◽

2020 ◽

Vol 7 (8) ◽

pp. 1410-1412

Author(s):

Weijie Zhao ◽

Chu Wang

Keyword(s):

Protein Design ◽

De Novo ◽

Protein Structures ◽

Computational Prediction ◽

Biological Functions ◽

Personal Experiences ◽

De Novo Protein Design ◽

And Function ◽

The University ◽

Opening Up

Abstract Search ‘de novo protein design’ on Google and you will find the name David Baker in all results of the first page. Professor David Baker at the University of Washington and other scientists are opening up a new world of fantastic proteins. Protein is the direct executor of most biological functions and its structure and function are fully determined by its primary sequence. Baker's group developed the Rosetta software suite that enabled the computational prediction and design of protein structures. Being able to design proteins from scratch means being able to design executors for diverse purposes and benefit society in multiple ways. Recently, NSR interviewed Prof. Baker on this fast-developing field and his personal experiences.

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De novo protein design enables precise induction of functional antibodies in vivo

10.1101/685867 ◽

2019 ◽

Cited By ~ 3

Author(s):

Fabian Sesterhenn ◽

Che Yang ◽

Jaume Bonet ◽

Johannes T Cramer ◽

Xiaolin Wen ◽

...

Keyword(s):

Protein Design ◽

De Novo ◽

Antibody Responses ◽

Design Algorithm ◽

De Novo Protein Design ◽

Complex Structural ◽

Syncytial Virus ◽

Functional Antibodies ◽

Novel Protein

AbstractDe novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a novel protein design algorithm, termed TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. Both in mice and non-human primates, cocktails of three de novo designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused pre-existing antibody responses towards defined neutralization epitopes. Overall, our de novo design approach opens the possibility of targeting specific epitopes for vaccine and therapeutic antibody development, and more generally will be applicable to design de novo proteins displaying complex functional motifs.

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Beyond de novo protein design — de novo design of non-natural folded oligomers

Current Opinion in Structural Biology ◽

10.1016/j.sbi.2004.07.001 ◽

2004 ◽

Vol 14 (4) ◽

pp. 512-520 ◽

Cited By ~ 91

Author(s):

Richard P Cheng

Keyword(s):

Protein Design ◽

De Novo ◽

De Novo Design ◽

De Novo Protein Design

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Biological Assembly of Modular Protein Building Blocks as Sensing, Delivery, and Therapeutic Agents

Annual Review of Chemical and Biomolecular Engineering ◽

10.1146/annurev-chembioeng-101519-121526 ◽

2020 ◽

Vol 11 (1) ◽

pp. 35-62 ◽

Cited By ~ 2

Author(s):

Emily A. Berckman ◽

Emily J. Hartzell ◽

Alexander A. Mitkas ◽

Qing Sun ◽

Wilfred Chen

Keyword(s):

Protein Design ◽

Biomedical Applications ◽

De Novo ◽

Building Blocks ◽

Specific Protein ◽

Therapeutic Agents ◽

Biological Functions ◽

Functional Protein ◽

Wide Range ◽

De Novo Protein Design

Nature has evolved a wide range of strategies to create self-assembled protein nanostructures with structurally defined architectures that serve a myriad of highly specialized biological functions. With the advent of biological tools for site-specific protein modifications and de novo protein design, a wide range of customized protein nanocarriers have been created using both natural and synthetic biological building blocks to mimic these native designs for targeted biomedical applications. In this review, different design frameworks and synthetic decoration strategies for achieving these functional protein nanostructures are summarized. Key attributes of these designer protein nanostructures, their unique functions, and their impact on biosensing and therapeutic applications are discussed.

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Recent Progress Using De Novo Design to Study Protein Structure, Design and Binding Interactions

Life ◽

10.3390/life11030225 ◽

2021 ◽

Vol 11 (3) ◽

pp. 225

Author(s):

Juan Ferrando ◽

Lee A. Solomon

Keyword(s):

Small Molecules ◽

Protein Design ◽

Protein Interactions ◽

De Novo ◽

De Novo Design ◽

Structure Design ◽

Protein Protein Interactions ◽

Design Studies ◽

De Novo Protein Design ◽

Artificial Protein

De novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity. Here, we will review recent examples of de novo design studies on binding reactions for small molecules, nucleic acids, and the formation of protein-protein interactions. We will then discuss some new structural advances in the field. Finally, we will discuss some advancements in computational modeling and design approaches and provide an overview of some modern algorithmic tools being used to design these proteins.

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