Docking to multiple pockets or ligand fields for screening, activity prediction and scaffold hopping

作者：Chen Yu Chen; Totrov Max; Abagyan Ruben^*

来源：Future Medicinal Chemistry, 2014, 6(16): 1741-1755.

DOI：10.4155/FMC.14.113

Background: Two recent technological advances dramatically reducing the rate of false-negatives in activity prediction by docking flexible 3D models of compounds include multi-conformational docking (mPockDock) and the docking of candidates to atomic property fields derived by co-crystallized ligands (mApfDock). Results: The mApfDock and mPockDock provide the AUC of 90.4 and 83.8%, respectively. The mApfDock gave better performance when compounds required large induced-fit pocket changes unseen in crystallography, whereas the mPockDock is superior when the co-crystallized ligands do not represent sufficient chemical and binding location diversity. Conclusion: Both approaches proved to be efficient for scaffold hopping; they are complementary when the coverage of the co-crystallized complexes is poor but become convergent when the complexes are diverse enough.

• 出版日期2014