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SynLinker is an integrated system to provide suitable linker candidates for novel recombinant fusion proteins. Many important biopharmaceuticals are recombinant fusion proteins, which comprise of two domains and a linker in between. Linkers have several functionalities. They can affect the fusion proteins in terms of protein expression, stability/folding, targeting to the cellular location, pharmacokinetic profiles as well as biological activity (Fig 1).

Fig 1: Functionalities of Linkers in Recombinant Fusion Proteins.

SynLinker content

SynLinker consists of 2150 natural linker sequences derived from PDB database and about 110 empirical linkers from public domain (Fig 2). The process to obtain natural linkers in SynLinker started from a non-redundant PDB chain set, among which the multi-domain proteins were confirmed by CDD, SCOP and CATH. About 2150 natural linker sequences were then assigned by CDD and DSSP and extracted from the multi-domain protein set. From literature research, about 50 empirical and artificial linkers were collected, which were categorized into flexible, rigid and cleavable linkers. From patent search, about 60 linkers from natural proteins and artificial design were collected. The natural linkers collected from patent search do not exist in the natural linker set obtained in the first approach.

Fig 2: SynLinker content.

Searching SynLinker

A series of searching criteria serve as filters for SynLinker. The user may specify PDB ID, protein name, the number of residues in a linker, and/or end-to-end distance of a linker conformation in Angstroms (Å), to search SynLinker. Additionally, the user can choose linker starting residue, ending residue, amino acid enrichment, amino acid depletion and/or sensitivity to protease as the desired linker properties in the recombinant fusion proteins. The query types can be applied separately or together.

Please Cite: Liu C, Chin JX and Lee DY (2015). SynLinker: an integrated system for designing linkers and synthetic fusion proteins. Bioinformatics, doi: 10.1093/bioinformatics/btv447 (link)

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SynLinker is free for academic and non-commercial use. For a commercial license please contact us.
The project is partly supported by the Next-Generation BioGreen 21 Program (SSAC, No. PJ01109405), RDA, Republic of Korea.
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