 Structure-based drug design, SPDD, has been making a comeback after being largely abandoned for decades due to its lack of success. However, recent advancements in computational biology and chemistry have allowed researchers to make significant strides in this area. In particular, the ability to accurately calculate the free energy of binding has improved significantly, allowing researchers to better understand the interactions between ligands and their receptors. Additionally, the development of homology models of receptors based on x-ray crystallography and other techniques has enabled researchers to more effectively tailor and screen virtual libraries with higher hit rates. Finally, the combination of multiple techniques such as x-ray crystallography, bioinformatics, and molecular modeling has proven to be highly effective in identifying potential drug candidates. This article was authored by Valir Launas, Tina Richel, Jan Kelder, and others.