A better way to design fusion protein drugs

March 23, 2016

New software developed at A*STAR could help scientists design sophisticated biopharmaceutical drugs that demand the joining of proteins together. The tool, which is freely available online, allows researchers and drug developers to input the protein fragments desired and pick the best 'linkers' accordingly.

Lead platform developer Dong-Yup Lee, a chemical engineer at the A*STAR Bioprocessing Technology Institute (BTI) and the National University of Singapore, says he is "very open to collaborating with other researchers, especially from biopharma companies, who are looking for suitable linkers for their synthetic fusion protein drugs."

Lee and his colleagues described the software in the journal Bioinformatics.

The choice of a suitable peptide linker can be complicated, and is often overlooked in the design of antibodies and other complex drugs or biotechnology tools that involve joining two different proteins. Yet with an unsuitable linker, the attached proteins might not fold properly. They might also be expressed at low levels, or have impaired activity.

To improve the process of linker selection, Lee and his colleagues developed a web-based platform called SynLinker, which contains a database of 2,150 naturally occurring peptide linkers plus another 110 artificial or empirical linkers. Users can search SynLinker by linker length, amino acid composition, solubility and other features that affect linker flexibility and function. After picking from multiple candidate linkers, users can then model their desired fusion protein constructs with each linker. "The prediction of a possible conformation of the fusion protein is a unique feature of SynLinker," Lee says.

Lee's team has used SynLinker to select suitable linkers for fusion enzymes that allow scientists to study human drug metabolism in laboratory model organisms. Lee explains that he and his colleagues are expressing these fusion systems in a yeast strain, and they are "currently being validated experimentally for functional testing via collaboration with the microbial group from BTI."

Similar bioinformatics tools existed, but have now ceased. The one called LINKER is no longer online, and the other, known as LinkerDB, is no longer being updated or improved. SynLinker is important to the biomedical research community as it provides the most current and thorough resource of its kind. "SynLinker is the only up-to-date available online resource for selecting linker candidates in synthetic fusion protein design," Lee says.

SynLinker is freely available online. "We also provide online help information and tutorial video to guide the users to use SynLinker," Lee says.

Explore further: Web tool helps researchers to obtain higher protein yields for a range of life sciences applications

More information: Chengcheng Liu et al. SynLinker: an integrated system for designing linkers and synthetic fusion proteins: Fig. 1., Bioinformatics (2015). DOI: 10.1093/bioinformatics/btv447

Related Stories

New computer model sets new precedent in drug discovery

November 18, 2014

A major challenge faced by the pharmaceutical industry has been how to rationally design and select protein molecules to create effective biologic drug therapies while reducing unintended side effects - a challenge that has ...

Making better enzymes and protein drugs

February 29, 2016

Natural selection results in protein sequences that are only soluble to the level that is required to carry out its physiological function. However, in biotechnological applications, we need these proteins to survive concentrations ...

Recommended for you

New analysis of big data sheds light on cell functions

October 26, 2016

Researchers have developed a new way of obtaining useful information from big data in biology to better understand—and predict—what goes on inside a cell. Using genome-scale models, researchers were able to integrate ...

Researchers identify genes for 'Help me!' aromas from corn

October 25, 2016

When corn seedlings are nibbled by caterpillars, they defend themselves by releasing scent compounds that attract parasitic wasps whose larvae consume the caterpillar—but not all corn varieties are equally effective at ...

Structure of key DNA replication protein solved

October 25, 2016

A research team led by scientists at the Icahn School of Medicine at Mount Sinai (ISMMS) has solved the three-dimensional structure of a key protein that helps damaged cellular DNA repair itself. Investigators say that knowing ...

Genome editing: Efficient CRISPR experiments in mouse cells

October 25, 2016

In order to use the CRISPR-Cas9 system to cut genes, researchers must design an RNA sequence that matches the DNA of the target gene. Most genes have hundreds of such sequences, with varying activity and uniqueness in the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.