Journal of Computer-Aided Molecular Design

, Volume 22, Issue 6, pp 507–521

A ligand’s-eye view of protein binding


DOI: 10.1007/s10822-008-9177-8

Cite this article as:
Clark, R.D. J Comput Aided Mol Des (2008) 22: 507. doi:10.1007/s10822-008-9177-8


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.


CoMFA COX-2 Cyclooxygenase HEPT Ligand alignment QSAR Reverse transcriptase Surflex-Dock Bioactive conformation 

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Tripos Informatics Research CenterSaint LouisUSA

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