Table 6.
Comparison of the advantages and disadvantages of various computer-aided drug design approaches
| Approach | Advantage | Disadvantage | |
|---|---|---|---|
| Ligand-based drug design (LBDD) | Quantitative structure–activity relationship314,315 (QSAR) | Understanding interactions between functional groups, convenient, does not require the structural information of a target | Descriptor selection, false correlations, enough known ligands |
| Pharmacophore modeling316,317 | Effective model, convenient, does not require the structural information of a target | Known ligands, less novelty; missing conformations | |
| Structure-based drug design (SBDD) | Virtual screening of ultra-large libraries224–226 | Novel scaffolds and chemotypes, higher chances of finding potent ligands | Substantial computational resources, compound synthesis |
| Virtual screening of focused libraries227–229 | Less demand for computational resources, compound easy to purchase, specific scaffolds or origins | Reduced diversity, less novelty | |
| Ensemble docking235–237 | Considering protein flexibility, improved enrichment factors, rescue of false-negative ligands | Increased computational burden, pose evaluation, false positive | |
| Energy-based pose evaluation248–252 | Improved scoring and ranking ability | Substantial computational burden, method validation target dependency |