Docking, virtual high throughput screening and in silico fragment‐based drug design

Abstract

• Introduction • Docking ‐ Protein and ligand flexibility ‐ Sampling algorithm ‐ Scoring functions ‐ Performance • Virtual high throughput screening ‐ Ligand‐based vHTS ‐ Structure‐based vHTS • In silico fragment‐based drug design ‐ Theoretical advantages of FBD ‐ Existing FBD methods ‐ Synthetic accessibility of molecules proposed by FBD • Conclusion Abstract The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high‐throughput screening and fragment‐based ligand design.