“The paper presents a rather critical review of computational methods for structure-based ligand design and virtual screening...”

The paper presents a rather critical review of computational methods for structure-based ligand design and virtual screening with a strong focus on drug discovery problems. It covers both the hit identification and lead optimization stages, which sets it apart from a number of other reviews.

Docking methods are widely used in basic and applied pharmaceutical research and many different algorithms and scoring schemes have been introduced. However, successful applications do generally require a fairly high level of expertise and experience. I believe what this review helps achieve is a focusing on promising application scenarios while avoiding some principal caveats.

It describes many different methods for the structure-based discovery of new active compounds and discusses exemplary applications in case studies. Importantly, it attempts to illustrate the pros and cons of various approaches.

Considering 3D protein structure information in the context of drug design and discovery immediately leads to an interest in docking methods. This is also where my interest in this area of research originated. However, finding new hits or leads via docking is far from being a routine process. We have succeeded in some cases and failed in others.