An association of virtual screening, docking and a good rescoring procedure is a well known technique to discover and design new lead compounds in medicinal chemistry.
For example, the same techniques were born in the last years, like virtual screening, docking as far as evolution of dynamic simulations, steered molecular dynamics (SMD) [ 2], or metadynamic studies.
The 'hit' rate of 17 25% displayed by our α1-AR pharmacophores is comparable to the 'hit' rates achieved using the structure based virtual screening technique of docking at the serotonin 5-HT1A and 5-HT4, D2pamine D2, chemokine CCR3 and tachykinin NK1 receptors [22], for which 'hit' rates varied between 12 21% (Ki values <5 µM).
Molecular docking is a virtual screening technique that scores compounds in a known or predicted binding site.
Rashad and Keller [ 71] used in silico techniques of virtual screening and docking studies for structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins.
In contrast with virtual screening techniques (e.g., QSAR or docking), HTS does not require prior knowledge about potential hits or 3D structures of involved molecular targets.
This framework thus greatly facilitates the application of virtual screening and docking and consistent storing and handling of data.
The first step is usually virtual screening by docking or the pharmacophore method.
As a main method of structure-based virtual screening, molecular docking is the most widely used in practice.
Virtual screening with docking was performed on one Linux PC (quadricore Intel 2.66 GHz, 2 GB RAM).
Based on this homology model, small molecule inhibitors of AAT then can be identified through the use of virtual screening, a computational technique that can prescreen vast databases of small molecule structures against a three-dimensional structure to see which of these dock into a chosen substrate-binding site.
