3D QSAR: Current State, Scope, and Limitations

Abstract

ConclusionAll evidence suggests that 3D QSAR techniques will continue to make a valuable con-tribution to the computer-assisted analysis of structure-bioactivity relationships. The search for new descriptors of 3D properties of ligands and innovative strategies to investigate the relationships between these properties and bioactivity continues to be a fruitful research enterprise. Increasing information from structural biology will provide valuable feedback to the hypotheses that form the basis of 3D QSAR methods.3D QSAR methods complement traditional QSAR based on physical properties. They offer the advantage that it is easy to calculate descriptors for most molecules, and the disadvantage that one must select a conformation and usually a superposition rule as part of the analysis.Because of their speed and accuracy, 3D QSAR methods complement calculations based on the structure of the ligand-macromolecular complex. Whereas the structure of at least one complex aids in the selection of the bioactive conformation and the align-ment of the molecules for 3D QSAR, a QSAR model can be derived much more quickly than calculations based on the complex. Frequently, it is just as predictive. Knowledge of the structure of the complex can also prevent unwarranted extrapolation from a QSAR model.It is expected that concepts from 3D QSAR will continue to impact the analysis of high-throughput screening structure-activity data and the diversity of compound collec-tions and combinatorial libraries.