Abstract submission open – FBDD DU 2022

We are pleased to announce that abstract submission for the 4th Fragment-Based Drug Discovery Down Under Conference 2022 is now open!

Important dates

Abstract submission deadline oral presentations:15 July 2022
Abstract submission deadline posters:12 August 2022
Registration open:20 June 2022
Registration close: 14 September 2022

Visit https://fbdddownunder.com.au/ to register your attendance.

We are looking forward to meeting everyone back in Melbourne from 28 to 30 September 2022!

Save the date – FBDD DU 2022

The next Fragment-Based Drug Design Down Under Conference will be held at Monash Parkville Campus, Melbourne from 28 to 30 September 2022

The conference will include workshops, scientific sessions and social events. There will be poster and oral presentation prizes for student and ECR delegates.

Topics to be covered are library design, fragment screening, structural biology, computation chemistry, fragment-to-hit-to-lead chemistry and success stories.

Submission deadlines:

  • Oral presentation abstracts – 15 July 2022
  • Poster abstracts – 12 August 2022

For more information, visit fbdddownunder.com.au.

A truly collaborative work – new paper on DsbA

Not one but five CFBD members from our three nodes published a paper on DsbA titled “Identification and characterization of two drug-like fragments that bind to the same cryptic binding pocket of Burkholderia pseudomallei DsbA” in Acta Crystallographica Section D.


Disulfide-bond-forming proteins (Dsbs) play a crucial role in the pathogenicity of many Gram-negative bacteria. Disulfide-bond-forming protein A (DsbA) catalyzes the formation of the disulfide bonds necessary for the activity and stability of multiple substrate proteins, including many virulence factors. Hence, DsbA is an attractive target for the development of new drugs to combat bacterial infections. Here, two fragments, bromophenoxy propanamide (1) and 4-methoxy-N-phenylbenzenesulfonamide (2), were identified that bind to DsbA from the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis. The crystal structures of oxidized B. pseudomallei DsbA (termed BpsDsbA) co-crystallized with 1 or 2 show that both fragments bind to a hydrophobic pocket that is formed by a change in the side-chain orientation of Tyr110. This conformational change opens a `cryptic’ pocket that is not evident in the apoprotein structure. This binding location was supported by 2D-NMR studies, which identified a chemical shift perturbation of the Tyr110 backbone amide resonance of more than 0.05 p.p.m. upon the addition of 2 mM fragment 1 and of more than 0.04 p.p.m. upon the addition of 1 mM fragment 2. Although binding was detected by both X-ray crystallography and NMR, the binding affinity (Kd) for both fragments was low (above 2 mM), suggesting weak interactions with BpsDsbA. This conclusion is also supported by the crystal structure models, which ascribe partial occupancy to the ligands in the cryptic binding pocket. Small fragments such as 1 and 2 are not expected to have a high energetic binding affinity due to their relatively small surface area and the few functional groups that are available for intermolecular interactions. However, their simplicity makes them ideal for functionalization and optimization. The identification of the binding sites of 1 and 2 to BpsDsbA could provide a starting point for the development of more potent novel antimicrobial compounds that target DsbA and bacterial virulence.

Read the full article here.

First Author paper for PhD student Sarah Müller

Congratulations to PhD student Sarah Müller from Griffith University who published a paper as first author. 

The Glitazone Class of Drugs as Carbonic Anhydrase Inhibitors—A Spin-Off Discovery from Fragment Screening

Most of the drugs we know target the activity of specific proteins that play an important role in the disease being treated. One of the big challenges in the discovery of new drugs is finding molecules that bind specifically to one target and not bind to other proteins too. This is necessary to avoid causing treatment side effects. Hence, drug discovery researchers are always on the lookout for ways to find better lead molecules.
We identified an old drug class called glitazones that target a new protein known as carbonic anhydrase II, an enzyme that helps to maintain pH levels in cells. Carbonic anhydrase comes in many different forms and has been a successful target for drug development for various diseases like glaucoma, heart failure and epilepsy.
The glitazone drugs, such as rosiglitazone, are used to treat Type II diabetes. However, because of the severe side effects caused by the use of glitazones they were taken off the market. Our findings suggest that the unintended targeting of carbonic anhydrase may be one reason for the side effects of these drugs. This shows how important it is to carry out research to fully understand the effect of drugs and can help future researchers in drug discovery.

The paper was published in Molecules in May 2021.

We are hiring – Biomolecular NMR spectroscopist/Structural Biologist

We have a postdoctoral position available for a Biomolecular NMR spectroscopist/Structural Biologist within the ARC Centre for Fragment-Based Design.

The exciting opportunity for a Research Fellow who will be working our Centre. The successful candidate will contribute to research on fragment-based drug design projects with a focus on a range of therapeutic targets across different areas such as infectious disease, cancer and diabetes.

You will have:

  • A PhD in structural biology with related research experience
  • Strong theoretical knowledge of NMR spectroscopy and its application in the analysis of biomolecules
  • Strong practical experimental skills in the characterisation of protein structures from experimental data
  • Prior knowledge and experience in data analytics is desirable
  • Experience with industry will be highly regarded

If you are ready to take the next step in your research career, we look forward to receiving your application.

ARC Discovery Project Success

Congratulations to CFBD CI Professor Sally-Ann Poulsen from Griffith University for being awarded an ARC Discovery Project grant worth $415,495 together with Professor Katherine Andrews (Griffith Institute for Drug Discovery, Sciences). The project Chemical probes to dissect the cell cycle of globally important parasites aims to develop new reagents, called chemical probes, to visualise key biological events in globally important pathogens. The team will use innovative chemistry to modify the building blocks of DNA and provide researchers with essential tools to ‘see’ DNA synthesis in order to study growth and replication of pathogens in combination with microscopy. This project expects to support a major technical advance that will address important gaps in our understanding of many pathogens (e.g. those that cause malaria and tuberculosis), at both the cellular and molecular levels. This should provide significant benefits by enabling researchers worldwide to identify new intervention opportunities that target unique aspects of pathogen biology (with Dr Martin Blume, Robert Koch Institute).

CFBD Deputy Director appointed Acting Theme Leader

Congratulations to CFBD Deputy Director A/Prof Ben Capuano for being appointed as Acting Theme Leader in the Medicinal Chemistry Department at the Monash Insitute of Pharmaceutical Sciences (MIPS).

Ben has taken over the position from Prof Peter Scammells who will now be focusing on his role as Associate Dean, Research, Faculty of Pharmacy & Pharmaceutical Sciences. Within CFBD, Ben leads the Fragment Elaboration theme. He is a synthetic medicinal chemist specialising in GPCRs.