Creative BioMart is a well-known expert who uses various protein domains as non-antibody scaffolds to produce synthetic binding proteins that have the ability to bind to molecules. With years of experience, we successfully designed single loop binding protein based on non-antibody scaffolds to precisely meet customer requirements.

Introduction of Protein Loops

Loops are fragments of protein chains that connect two modeless regions of regular secondary structure. They are usually located on the surface of the protein in the solvent-exposed area and play an important role in function, including in protein-protein interactions, recognition sites, signal cascades, ligand binding, DNA binding, and enzyme catalysis. However, structural characterization of protein loops is difficult because of their conformational flexibility and relatively poor conservation in multiple sequence alignments. Loops usually involve the functional regions of proteins, and accurate methods for predicting the structure of three-dimensional loops can be valuable tools for the design of new proteins from scratch or small molecules involving protein loops in the binding interface. According to reports, many circuit modeling methods from scratch have achieved results in reconstructing circuits in high-resolution crystal structures. The latest AlphaFold2 has achieved extraordinary performance in protein structure prediction. In addition, many functional loop structures have been reported in enzymes. These peptide fragments promote catalysis by positioning functional groups at the active site and changing the reaction environment.

Fig 1. Time scales of loop dynamics in proteins. (Papaleo E, et al., 2016)

Services

Loops play an important role in protein folding and stability. In addition, the loop usually determines the functional specificity of the protein molecule. Because of their role in protein function, loops are also an important consideration in protein engineering. Because loops are usually located on the surface of protein structures, they are susceptible to the insertion and deletion of amino acids, and their structure is also difficult to predict. As a leading service provider of protein engineering, Creative BioMart models missing loops to design proteins with complex functions (active sites and binding interfaces) and develops a variety of methods to accurately predict protein loop structures. Our single loop protein platform is widely used in the areas of protein function, drug design and docking of small molecules.

The design of complex protein molecules seems to inevitably require the ability to design structured loops with high precision. With our help, monocyclic proteins that meet certain structural and functional requirements will be used in normal biological processes. Importantly, loop modeling is a crucial step in homology modeling. We combine protein loops classification and database search methods to predict loops structure, and provide several cycle modeling methods, which can be divided into:

• Ab initio method: this method determines loop conformations computationally, through the exploration of the conformational space. It is dependent on energy optimization techniques and are consequently highly time consuming.
• Data-based method: this method depends on the geometry of the flanks (the area before and after the modeled loop) residues and the database used to mine candidates. It is suitable when there are fragments similar to the ring of interest in the database.
• Hybrid loop modeling method: this method combines Ab initio and data-based methods to improve the quality of loop predictions, which first performs data-based search to find fragments shorter than the loop of interest and obtains structural informations. Then it applies ab initio methods to generate fragments of correct length.

Based on the protein engineering platform, we have successfully designed a variety of platforms for different applications to produce special proteins. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

References

1. Shehu A, Kavraki LE. (2012) Modeling Structures and Motions of Loops in Protein Molecules. Entropy. 14(2): 252-290.
2. Choi Y, Agarwal S, Deane CM. (2013) How long is a piece of loop? PeerJ. 1: e1.
3. Papaleo E, Saladino G, Lambrughi M, et al. (2016) The role of protein loops and linkers in conformational dynamics and allostery[J]. Chemical reviews. 116(11): 6391-6423.

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