Professor Hirst's research focuses on the application of computational chemistry to challenging problems in chemistry and biology. His research spans a wide range, from the quantum chemistry of small molecules and the spectroscopic properties of proteins, to the application of state-of-the-art statistical and computer science methodology to problems in bioinformatics, drug design and sustainable chemistry. Insights from the work on formamide and other small amides have been applied to studies of proteins and have led to significant improvements in the calculation of the circular dichroism of proteins from first principles. The success of Hirst's quantum chemical research is reflected in the number of collaborations with biomolecular experimentalists. His calculations on protein circular dichroism spectroscopy, a key technique in structural biology, are the most accurate to be published. Another aspect of Hirst's research focuses on the study of protein-ligand interactions, using techniques including QSAR, machine learning, neural networks, docking, molecular dynamics (MD) simulations and quantum chemistry.