Docking protocols

Furet et al. described the discovery of a novel, potent and selective kinase CK2 inhibitor by a high-throughput docking protocol [250]. A large subset of the Novartis corporate database with 400 000 compounds was flexibly docked using DOCK 4.01 [93, 117]... 

Zhao et al. implemented a structure-based docking protocol to narrow down 500 compounds from a database of 57 compounds in their pursuit of FKBPs inhibitors (89). A novel scaffold was designed using the information obtained from the binding mode analysis of a known weak binder. To avoid any scoring function shortcomings, three scoring functions were used to select the 500 compounds. Of these, 43 were synthesized and tested to identify one potent inhibitor in a mouse peripheral synthetic nerve model. 

For the structure calculation, 5000 binding poses of EpoA were generated by non-restraint docking of its NMR-derived conformation into the binding site of the EC-derived 3D structure of tubulin (complex TB). The docking protocol was designed to sample tubulin conformations that differed from the starting EC-derived... 

The shape-based virtual screening protocols performed better than the docking protocols overall. Finally, a consensus rank-byvote selection technique was used and the five best compounds were selected from the hits for synthesis and for determining antiviral activity. Remarkably, two of the five compounds (Fig. 13) showed activity at low micromolar ranges (0.022 pg/mL and 0.058 pg/mL, respectively). 

Induced-fit docking protocol from Schrodinger used to dock into Mt-GuaB2-IMP homology model Lead compound 7,759,844 IC = 0.603 pM docked to show binding orientation and rationalize SAR Usha etal. (92)... 

Mozziconacci et al.61 used Cox-2 as their test case. The first part of the paper looks at the selection of the optimal parameters for the docking protocol (here using DOCK), followed by a consensus scoring approach. Having optimised the protocol with known ligands, a large (13,711) virtual library was screened. Of the 12 compounds selected and available for assay, 4 had IC50 s < 1 /iM. 

Table 4.2 Protein kinase A virtual screening rankings obtained for the rigid, ensemble, and flexible docking protocols.

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