High-throughput screening (HTS) is commonly used in early stage drug discovery to identify potential binders or hits. HTS involves taking a large library of molecules and screening them against a target (e.g. a protein). Hit rates in HTS campaigns are often low, simply due to how vast chemical space can be and the complexity of therapeutic targets. One common strategy in fragment-based drug discovery (FBDD) projects is to conduct the screen using smaller molecules (fragments) to cover a larger portion in chemical space which may lead to higher hit rates. Often in this approach hits tend to be weak binders, but they can serve as a starting point for building a potential lead molecule. From the pool of hits, medicinal chemists may find a desirable starting scaffold or they can build up new molecules by connecting fragments together in hopes to improve binding affinity. While doing this optimization, chemists must gain an understanding of where and how their molecule binds to their target protein to guide their efforts to optimize the compound's binding or selectivity. Some experimental approaches to gaining structural insight on ligand binding include X-ray crystallography, nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). Each of these approaches present its own set of benefits and challenges but most are costly, time-consuming and difficult. For example, X-ray crystallography provides structural information with near atomic-resolution, but obtaining high resolution crystal can be extremely challenging. Especially with FBDD, resolving the binding mode(s) for small molecules and fragments proves challenging as fragments often bind in several different configurations. This often produces X-ray structures which have ambiguous densities around the bound ligand or are generally in too low resolution to definitively resolve the fragment binding mode(s). Here, with these ambiguous densities in the crystal structures, computational approaches may aid in the design process by resolving ambiguities through predicting fragment binding modes. Computational methods like docking or molecular dynamics (MD) simulations are some common approaches used in helping to determine fragment binding modes. If these techniques are accurate enough, computational chemists can apply them to make sense of partial occupancy data and help rescue structure-based design work on fragments that might otherwise have stalled.