Folding is a fundamental part of protein structure. Understanding the emergence of new protein folds is an important step in understanding the rules governing the evolution of protein structure and function and in developing tools for protein structure modeling and design. With the support of our advanced protein engineering platform established for many years, Creative BioMart provides a comprehensive customized knowledge-based novel protein folds design service to design novel protein topologies.

Protein sequences can vary in size from tens to thousands of amino acids. But this chain has to be folded correctly into a unique three-dimensional structure for it to work. Predicting how proteins fold from their sequences has developed into a research hotspot for scientists. A major breakthrough in the design of novel protein folds has been the computational design of a family of α-helical bundles with right-handed supercoiled topology. Before this work, the structure of trimeric or tetrameric helical bundles with right-handed supercoiled topology was not known. The design of novel folds can now create completely new proteins with arbitrarily chosen three-dimensional structures. For example, scientists successfully engineered protein topologies not observed in nature and set out to design a 93-residue α/β protein with this new fold.

Fig 1. De novo protein design for novel folds using guided conditional wasserstein generative adversarial networks. (Ljubetič A, et al., 2017)

Services

In fact, the tertiary structure of only a small fraction of polypeptide sequences is known, with fewer than 2,000 native protein folds. Expanding the number of protein folds and good molecular models with topology is an urgent task. Creative BioMart uses advanced computational modeling or modular construction principles (such as oligomeric domains) to design novel protein topologies. The engineered proteins exhibit several interesting features, such as extreme stability, designability of 3D topology, and folding pathways. Our novel protein design service provides researchers with new insights into the mechanisms of protein folding and construction, as well as the possibility to organize protein structures in a controlled manner and create novel biomimetic assemblies.

Our scientists are able to calculate novel amino acid sequences for any known geometrically stable protein fold, and our ultimate goal is to design novel protein structures with entirely new biological functions. Supported by computational methods, we have successfully developed multiple novel protein folds. For example:

• β-strand fold

We can assemble β-strands into other structures such as β-hairpins, β-turns and β-barrels or combine with α-helices to form α/β hybrid structures. Furthermore, the protein folds into symmetrical β-clover folds through the process of gene duplication and fusion.

• Design of α-peptides with unnatural amino acid units

By incorporating unnatural amino acids into the polypeptide backbone, new functions can be created by changing their structure. Optically active non-proteinogenic α-amino acids designed by methods such as bioresolving routes and rhodium- or ruthenium-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives are very popular as important tools for protein engineering and peptide-based drug discovery.

Service Principle

Creative BioMart is based on innovative, pragmatic and honest, adhering to the tenet of "Quality is our life, providing customers with the best quality service", providing customized services to customers around the world.

We will be glad to discuss details of intended interaction studies with you and develop experimental strategies/methods tailored to your requirement. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, Monday to Friday. If you are interested in our services, please do not hesitate to contact us for more information or to discuss in detail.

References

1. Karimi M, Zhu S, Cao Y, et al.. (2020) De novo protein design for novel folds using guided conditional Wasserstein generative adversarial networks[J]. Journal of chemical information and modeling. 60 (12): 5667-5681.
2. Fernandez-Fuentes N, Dybas J M, Fiser A. (2010) Structural characteristics of novel protein folds[J]. PLoS computational biology. 6 (4): e1000750.

• Knowledge-Based Membrane Protein Design
• Knowledge-Based Preorganized Structure Design
• Knowledge-Based Secondary Structure Self-Assembly Design
• Knowledge-Based Single-Chain Protein Design