John Shelley delivered this comprehensive presentation on the application of computer modelling in drug formulation. With over two decades of experience at Schrodinger LLC, Shelley focused on the potential impact of molecular modelling on drug formulation, an area not heavily used in the field.
Shelley began by providing an overview of Schrodinger's background and the types of modelling they specialise in, including molecular modelling and machine learning. He highlighted how understanding the internal structure of drug formulations is often difficult to characterise experimentally. Shelley explained that molecular modelling could bridge this gap by providing detailed insights into the internal structure of drug formulations.
He then discussed Schrodinger's software platform, which supports structure-based modelling and collaborative informatics. This platform allows for real-time data sharing and decision-making among scientists from different disciplines. Shelley also touched on the various techniques used in physics-based modelling, ranging from quantum mechanics to atomistic genetics, which enable quantitative predictions of drug-protein binding.
Shelley presented several case studies, including crystal structure prediction, API encapsulation by cyclodextrin, and excipient selection for ASD formulation. He discussed a collaboration with AbbVie on amorphous solid dispersion delivery of small molecule drugs, where molecular modelling helped understand and solve complex formulation problems.
The main part of Shelley's talk focused on lipid nanoparticle (LNP) modelling for mRNA delivery, inspired by the Pfizer-BioNTech vaccines. He detailed the simulation process, from the initial formation of LNPs in an acidic ethanol-water mixture to their behaviour under blood pH conditions. Shelley highlighted the challenges of bioavailability and endosomal escape, where only a small percentage of RNA gets translated. He shared promising results from simulations that showed both successful and unsuccessful RNA release, indicating the potential for further research and optimisation.
This presentation underscored the value of molecular modelling in drug formulation, advocating for its broader adoption to enhance the efficiency and effectiveness of drug development.
