Throughout my career, I have deliberately combined theory and software development with direct application to biology and drug discovery. In the former area, I have made major advances in understanding the role of water in drug design, securing a £600,000 research grant from the UK’s Medical Research Council to start a research group focused on water in drug design and publishing a number of first/single author papers on the statistical thermodynamics underlying hydration phenomena. In the latter area, I have developed a number of small-molecule inhibitors as part of collaborative academic drug discovery projects,including: RAD51 recombinase, Aurora-A kinase, Polo-like kinase 1, and HIV-1 protease. More recently, I have worked specifically on the development of novel free energy methods for drug design. My research group showed that free-energy changes can be partitioned to estimate contributions from specific atoms or chemical groups and that this can be used to understand the drivers of binding affinity in a way that is useful for drug discovery