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