A ligand's-eye view of protein binding.
Docking tools created for structure-based design and virtual screening have also been used to automate ligand alignment for comparative molecular field analysis (CoMFA). Models based on such alignments have been compared with those obtained based solely on shared ligand substructures, but such comparisons have generally failed to distinguish between conformational specification (alignment in the internal coordinate space) and embedding in a shared external frame of reference (Cartesian alignment). Here, large sets of inhibitors were docked into two cyclooxygenase and two reverse transcriptase crystal structures, and the poses generated were evaluated in terms of the CoMFA models they produced. Realigning the conformers obtained by docking by rigid-body rotation and translation to overlay their common substructures improved model statistics and interpretability, provided the protein structure used for docking was reasonably appropriate to the ligands being considered.
Clark
Robert D
RD
Tripos Informatics Research Center, 1699 South Hanley Road, Saint Louis, MO, 63144, USA. bclark@tripos.com
D051546:Cyclooxygenase 2 / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
D008024:Ligands; D051546:Cyclooxygenase 2; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase