Collaboration to Drive NMR Structural Biology Studies
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We spoke to Dr Joanne McCudden, Head of Business Development at Domainex to learn more about the company and their involvement in the drug discovery programs.
AB: Can you tell me more about Domainex and the services you provide?
Joanne McCudden (JM): Domainex is a UK biotech company that operates a hybrid business model. This means that it provides drug discovery services and technologies to progress its clients’ programmes and to generate revenue; and the revenue generated enables it to develop its own therapeutic pipeline, with minimal additional investment required.
Domainex’s service business includes not only its proprietary Combinatorial Domain Hunting technology, for the identification of expressible domains of protein drug targets, but also a full raft of capabilities essential for the completion of a target to candidate drug discovery programme.
- Protein production for use in structural studies and/or assay development. For some programmes, protein produced will be sent to ZoBio for NMR-based analysis; which will provide crucial structural information to help inform drug discovery programmes and decision making in compound design.
- Biochemical assay development for compound screening
- Bespoke cell assay development to enable secondary compound screening and probing of biological pathways
- Hit identification using virtual means or fragment-based approaches
- Medicinal chemistry
- Computational chemistry
- DMPK testing
AB: Can you tell me a little more about Domainex's involvement in FORMA Therapeutics' Drug Discovery Programs?
JM: Domainex and ZoBio are working closely together to help progress a number of FORMA’s cancer drug discovery programs. FORMA has a very exciting and ambitious approach to drug discovery research, which is to explore broad drug target classes in parallel. In Forma’s first five years, they explored over 110 targets across their core focus areas of tumor metabolism, epigenetics, protein homeostasis and other essential protein-protein interactions. Of course, some of the targets investigated by FORMA are more challenging than others. This is where ZoBio and Domainex come in, as we are able to de-rate limit challenging early drug discovery steps, by utilising our proprietary technologies and know-how. More specifically, this means:
For protein where expression in E. coli is not the key challenge, ZoBio will produce the required protein for use in structural studies.
Where expression is a particular challenge, Domainex will utilise its Combinatorial Domain Hunting (CDH) technology (http://www.domainex.co.uk/proteinexpression.asp) to identify domain constructs of a protein target, which can be expressed in E. coli in the soluble fraction and which when purified, exhibit native folding. Traditional methods of molecular biology will enable 10-100 protein constructs to be evaluated at once. Domainex’s CDH technology enables 20,000-120,000 different constructs of the target protein to be screened at once for optimum characteristics! Typically the best 5 protein constructs identified will be purified and progressed into structural studies.
The produced protein is then used by ZoBio for NMR studies. ZoBio is a world leading expert in protein nuclear magnetic resonance (NMR), which can be used to elucidate the molecular basis for compound-target interaction, to complement X-ray crystallography approaches. NMR is currently the only alternative to crystallography capable of elucidating atomic resolution, 3D structural information. It is therefore key in the targeting of more challenging drug targets.
AB: How closely will you be working with ZoBio during the programs?
JM: Domainex and ZoBio will be working in close partnership, as both companies have different skill sets and capabilities to bring to the project. There has already been cross fertilisation of ideas between the parties, which is very exciting. The whole is definitely greater than the sum of its parts in this collaboration.
AB: How does your partnership with ZoBio strengthen the companies’ offerings?
JM: ZoBio is the world leader in the use of NMR for drug discovery. As NMR is really the only option for 3D structural information when crystallography can’t be utilised, it is extremely powerful for novel and challenging drug targets. Domainex and ZoBio are working together well on FORMA Therapeutics Drug Discovery programs and hope to continue in this guise with other clients in the not too distant future.
AB: What do you expect to see as the biggest challenges during the programs?
JM: I think we have already overcome the biggest challenge, which is being honest and open when any problems crop up. It’s too easy to bury issues and to try to resolve problems on your own, in an attempt to save face. However, between ZoBio, Domainex and FORMA, we have worked together to overcome problems. We all have different expertise and capabilities, and different ways of looking at things. It is so much better scientifically to share ideas, but it is also a much more pleasant working relationship when you do!
Dr Joanne McCudden was speaking to Ashley Board, Managing Editor for Technology Networks.