Designer proteins for new bio-tech applications
An EU-funded project has developed a technique to design and synthesise highly stable proteins. The approach enables proteins to be made from scratch, tailored to carry out specific tasks for advances in fields such as biomedicine and biotech - boosting Europe's competitiveness.
© Gustav Oberdorfer, Possu Huang, 2014
Protein molecules are becoming increasingly essential for use in the fields of biomedicine and biotechnology. In medicine, proteins are replacing small molecule drugs, providing more effective and targeted treatment.
They are also being used as biocatalysts in industrial processes, reducing the environmental impact of advances in biotechnology. However, producing bespoke proteins with functionality and structure that is tailored for a specific application is no easy task.
The EU-funded ASR-COMPENZDES project has developed a new method to design and produce proteins. This takes advantage of sophisticated computational modelling tools to make new helical protein structures with unprecedented stability.
The newly designed proteins are stable at temperatures above 95 °C and in strong denaturing conditions. This makes their applications wider ranging than traditionally developed proteins, or those found in nature.
‘We have developed a robust technology that can build alpha-helical protein structures from scratch,’ says Gustav Oberdorfer of the University of Graz in Austria. ‘We can design a protein and pack its core really well, so that it becomes very stable. We can then try to adjust its functionality so it can be used in biomedicine or biotechnology as a drug, enzyme or nanomaterial.’
To design proteins, ASR-COMPENZDES combined equations developed in 1953 by Francis Crick, UK molecular biologist, biophysicist and neuroscientist, with modern computational methods. The equations accurately describe helical protein structures and, with the aid of today’s computing advances, can determine the amino-acid sequence needed to create a desired protein.
This bottom-up innovative approach can produce proteins with specified structures and functions. With the amino-acid sequence laid out, a DNA construct can be created that encodes for the designed protein to be produced.
Proteins for biomedicine and biotechnology
Proteins and antibodies used in biomedicine are often relatively unstable and must be transported and stored under the correct conditions. With the results of the ASR-COMPENZDES project, these issues are not a concern, and designed medications and treatments which could result from this new technique have the potential to reach more patients worldwide. Highly stable proteins can also be used more widely in medical diagnostics, bioindustry and biotechnology applications.
‘These highly stable proteins can be designed to suit many applications,’ says Oberdorfer, whose research was funded through the EU’s Marie Skłodowska-Curie actions programme.
‘We hope they will play a key role as biocatalysts and help reduce reliance on organic solvents and harsh reaction conditions. This will help make industrial processes greener and more environmentally friendly.’
The project led to a number of publications in international journals and the involvement of students both in Europe and the US. The results have been presented at international conferences. Some aspects to further fine-tune the technique to create bespoke proteins are now being supported with additional research grants.