Structure-Based Virtual Screening

Drug discovery and development is an expensive and timeconsuming process; taking from identification and validation of disease target through lead discovery and optimisation to clinical tests and regulatory approval. High-throughput in silico screening techniques offer an enormous benefit to drug discovery being both fast and practical for a seamless integration into daily research routines.

Structural genomics and high-throughput X-ray crystallography initiated a growth in the number of available X-ray structures that enabled structure-based virtual screening approaches to be dominant techniques in drug discovery. Ligand-supported homology modelling provides improved 3D structures in quality to further promote the application of structure-based methods.

Up to date many success stories and excellent reviews have been published revealing the importance of docking preparation and drawing attention to protein conformation, protonation states or tautomerism. Evaluation and ranking of predicted ligand conformations proves to be another crucial aspect of structurebased virtual screening. As the incorporation of the protein flexibility in docking calculations still reserves some untapped possibilities further improvements are expected in this field.

Here, we provide a full-length review of structure-based virtual screening approaches supporting our views by various case studies. The applicability and the performance of structure-based virtual screening processes in industrial environment are also demonstrated through some in-house studies. Hereby a picturesque review of structure-based virtual screening from the protocol development to its application focusing on the critical aspects is given.