Figure 4.

Summary of a canonical in silico fragment-based drug discovery (FBDD) pipeline, highlighting the applicability of different molecular simulation-based approaches. For each computational methodology, the simulation timescale that is required is reported, as well as the main (black dot) or secondary (white dots) applications. The table highlights the differences between approaches that can provide cross-cutting support to many FBDD phases (e.g., Markov state models; MSMs) from those that, because of their specificity and complexity, have a more focused use (e.g., free energy perturbation; FEP). Abbreviations: HT-SuMD, high-throughput supervised molecular dynamics; MSMD, mixed-solvent molecular dynamics; NCMC, nonequilibrium candidate Monte Carlo; SMD, steered molecular dynamics.