Towards improving compound selection in structure-based virtual screening

Structure-based virtual screening is now an established technology for supporting hit finding and lead optimisation in drug discovery. Recent validation studies have highlighted the poor performance of currently used scoring functions in estimating binding affinity and hence in ranking large datasets of docked ligands. Progress in the analysis of large datasets can be made through the use of appropriate data mining techniques and the derivation of a broader range of descriptors relevant to receptor–ligand binding. In addition, simple scoring functions can be supplemented by simulation-based scoring protocols. Developments in workflow design allow the automation of repetitive tasks, and also encourage the routine use of simulation-based methods and the rapid prototyping of novel modelling and analysis procedures.