Receptor-based 3D QSAR analysis of estrogen receptor ligands - merging the accuracy of receptor-based alignments with the computational efficiency of ligand-based methods

摘要: One of the major challenges in computational approaches to drug design is accurate prediction binding affinity biomolecules. In present study several methods for a published set estrogen receptor ligands are investigated and compared. The modes 30 were determined using docking program AutoDock compared with available X-ray structures receptor-ligand complexes. On basis results an interaction energy-based model, which uses information whole ligand-receptor complex, was generated. Several parameters modified order analyze their influence onto correlation between affinities calculated energies. highest coefficient (r2 = 0.617, q2LOO 0.570) obtained considering protein flexibility during energy evaluation. second method combination receptor-based 3D quantitative structure-activity relationships (3D QSAR) methods. ligand alignment from simulations taken as comparative field analysis applying GRID/GOLPE program. Using derived water probe smart region definition (SRD) variable selection, significant robust model 0.991, 0.921). predictive ability established further evaluated by test six additional compounds. comparison generated traditional CoMFA ligand-based 0.951, 0.796) indicates that QSAR able improve quality underlying model.