ABSTRACT
Leveraging artificial intelligence and deep learning to generate proteins de novo has unlocked new frontiers of protein design. This approach can be used to design bespoke binders that target specific proteins and domains. However, generating successful binders can have a low in silico success rate, often requiring thousands of designs and hundreds of GPU hours to obtain enough hits for experimental testing. There is a lack of efficient open-source pipelines designed for high-performance computing (HPC) systems that can maximise hardware resources and parallelise the workflow efficiently.

To address this challenge, we have developed ‘ProteinDJ’ - an open-source implementation of a protein binder design workflow that is deployable on HPC systems using the Nextflow orchestration domain-specific language and Singularity containerisation. It efficiently batches and parallelises the workload across both GPUs and CPUs. ProteinDJ is designed to be modular and includes multiple protein design software packages. ProteinDJ democratises protein binder design through a robust and user-friendly implementation and provides a framework for future protein design software pipelines.

BIOGRAPHY

Dr Josh Hardy is an expert in structural biology, with a particular focus on single-particle cryo-electron microscopy (cryo-EM). He applies cryo-EM to investigate the three-dimensional structures of proteins, aiming to understand their roles in human health and how mutations can lead to disease.

Josh completed his PhD in 2019 at the Biomedicine Discovery Institute, Monash University, where he used cryo-EM to determine structures of viruses with significance in both human health and biotechnology. In 2020, he joined WEHI as a joint postdoctoral researcher in the laboratories of A/Prof. Isabelle Lucet and A/Prof. Jeff Babon, where he began studying the structures of pseudokinases and cytokine receptors. In 2022, he was awarded an NHMRC Emerging Leadership 1 Fellowship.

Josh is committed to cryo-EM education and training. He established the Training in Electron Microscopy Processing and Optics (TEMPO) program at WEHI and has delivered guest lectures at cryo-EM workshops hosted by Bio21 and Monash. He also serves as Chair of the Ian Holmes Imaging Centre User Committee at Bio21 and is a member of the ARC Training Centre for Cryo-EM of Membrane Proteins.