Single Loop Protein Design

Protein loops frequently adopt specific conformations that are important to protein function. In natural proteins, many functional sites contain residues located in loops, and protein-protein interactions are always mediated by loops. As an expert in the protein design market, Creative Biolabs is committed to engineering the precise geometries, fine-tuned energetics, and subtle dynamics of proteins, as well as providing single loop protein design services for worldwide clients. Our rational design includes manual, computational and bioinformatic techniques for protein modification and de novo design.

Protein loops are irregular regions that connect two secondary structure elements. This fragment is often found in the solvent-exposed areas of the protein's surface and plays key roles in various activities, such as enzyme reactions, ligand binding, and interacting with other biological objects. Despite the lack of patterns, they are not completely random architectures. Many structures of functional loops have been reported in enzymes. These peptide fragments contribute to catalysis by positioning functional groups in the active site and changing the reaction environment. Virtually, loops are much more common in enzyme active sites than they are in general sites. A typical example is ketosteroid isomerase, where the arrangement of a general base (Asp38) by a structured loop is evaluated to show a 1700-fold effect on kcat.

Important applications of loops design. Fig.1 Important applications of loops design. (Kundert, 2019)

Protein functional sites, such as active sites and binding interfaces, are usually built from structured loops, shaped by the complicated requirements of protein functions. Despite their importance, their structure remains difficult to predict. At Creative Biolabs, we pay close attention to the design of protein function. Computational protein design, sometimes coupled with directed evolution, has been used to place catalytic groups, modify shape-complementary binding interfaces, and switch between different conformations. And these functions are normally performed by structured loops in natural proteins, probably because loops can access a wider range of conformational states with greater variation in rigidity or flexibility.

Schematic of a generic loop design protocol. Fig.2 Schematic of a generic loop design protocol. (Kundert, 2019)

Most protein loop structural prediction methods take samples on local loop segments and score them. Particularly, protein loop classifications and database search manners depend heavily on local properties of loops. Here, we have successfully applied database search methods in the realm of loop structure prediction and our scientists define loop design as the problem of predicting sequences. With the help of us, single loop proteins that satisfy certain structural and functional demands will be harvested for normal biological processes.

Loops in protein structures are significant because they not only interconnect secondary structural elements and change the direction of polypeptide chain’s propagation, but also, they harbor the active site residues. For this reason, it seems inevitable that the design of complex protein molecules will require the competent ability to design structured loops with high accuracy. As a reliable supplier in the synthetic protein engineering field, Creative Biolabs offers advanced single protein design services to obtain synthetic proteins with high affinity or specificity by rational strategies and proven computational methods. If you’re interested in our services, please don’t hesitate to contact usor directly send us an inquiry.


  1. Kundert, K.; et al. Computational design of structured loops for new protein functions. Biol Chem. 2019, 400(3): 275-288.

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