Experimentally hotspots can be defined as regions on the protein surface where crystallographic fragments aggregate. Consensus sites of solvent molecules were identified using mixed solvent crystallography (MSCS). However, alongside crystallography, NMR, and other biophysical approaches such as SPR or WAC-MS are commonly used for fragment screening. Although druggability indices have been created from NMR data, it is challenging to deduce the strength of specific key interactions from experimental approaches. Molecular simulation approaches such as SILCS or MixMD can be used but are computationally very demanding.