Structural Biology and Biochemistry (SBB) Theme Seminar

Title: Leveraging AI for Enhanced Drug Discovery: Perspectives on Antibody Engineering and Small Molecule Pharmacokinetics

Speaker 1: Dr Yoochan Myung

Abstract:  In 2023, the FDA reached a significant milestone by approving 71 new therapeutic drugs, marking an all-time high. Small molecule drugs dominated the majority of these approvals, although biologics, including antibodies, accounted for almost half of all approvals since 2022, underscoring the increasing importance of biologics in disease treatment.

Since early 2010, there have been signs of breaking the Eroom’s law, which traditionally dictated that the cost of developing a new drug doubles every nine years. This is likely attributed to advancements in information technology, particularly the utilisation of big data and AI techniques. The emergence of AI and data-driven approaches has ushered in a renaissance period in drug discovery, revolutionising traditional methodologies through in silico methods.

Major pharmaceutical companies face challenges, with almost half of clinical trial candidates terminated due to non-clinical toxicology and PK issues. Similarly, improving affinity maturation in antibody engineering remains a key bottleneck, crucial for enhancing binding affinity and specificity to pathogens.

While numerous AI-based approaches have evolved, current methodologies still suffer from limitations such as performance issues and a lack of comprehensive testing and validation. These deficiencies cast uncertainty on the credibility of available tools.

Today, I will delve into the application of AI in predicting pharmacokinetic properties and binding affinity in antibody-antigen interactions. Additionally, I will introduce in silico tools aimed at enhancing the pharmacokinetics of small molecule drugs and predicting binding affinity and its changes upon mutations in antibody engineering.

Bio: Yoochan Myung is a Postdoctoral Research Fellow at The University of Queensland, Australia. Yoochan's work focuses on developing cutting-edge deep learning-based approaches for antibody engineering and vaccine design under the supervision of David Ascher. His research is aimed at advancing our understanding of molecular interactions to improve therapeutic antibody design and drug development processes.

Title:  Making use of cryo-EM to inform next-generation vaccines and therapeutics

Speaker 2: Dr Ariel Isaacs

Abstract: Henipaviruses (HNVs) are an emerging viral genus with pandemic potential. These viruses are highly pathogenic and cause annual outbreaks in India and Bangladesh. Instances of HNV spillovers to humans have also been documented in Australia, China, Malaysia, Singapore and the Philippines. The threat of these viruses is exacerbated by the lack of approved human vaccines or therapies. HNVs enter cells through binding to receptors by an attachment (G) glycoprotein, followed by fusion of the viral and host membrane, mediated by the fusion (F) glycoprotein. As such, these two antigens are the major targets in both vaccine and therapeutic designs. In our work, we made use of cryogenic electron microscopy (cryoEM) to determine the structures of the F proteins of two novel HNVs, Langya (LayV) and Mojiang (MojV) viruses. We then leveraged this structural information to inform vaccine designs with the potential for broad-spectrum reactivity against a wide variety of HNVs. Furthermore, we identified antibodies that target LayV and MojV and identify the structure of a novel epitope within LayV G. Our work carries implications into vaccine and therapeutic development for HNVs, with the overall aim of improved pandemic preparedness against these emerging viruses.

Bio: Dr Ariel Isaacs is a postdoctoral research fellow at SCMB UQ, where he contributes to the development of the molecular clamp technology for a wide variety of emerging viruses. Ari has a special interest in henipaviruses, with a primary focus on vaccine development & therapeutic discovery. He makes use of cryogenic electron microscopy and functional assays to design next-generation, broad-spectrum vaccines and therapeutics to mitigate henipaviral disease. Ari was recently awarded an MRFF EMCR grant and an NHMRC Ideas grant to develop such vaccines and therapies that could offer protection against a wide variety of henipaviruses.