dprada
commented
3 years ago The paper has a not so short revision of the docking methodologies, describing strengths and defects. Check that almost every shortcoming and downside mentioned by Zoe Cournia and co-authors can be applied to classical pharmacophore models:
- Desolvation (ligand and protein) ---> I would say interfacial explicit waters
- Entropic penalties (ligand, protein, and water) ---> I would say entropic contributions to pharmacophores.
- Conformational strain (ligand and protein) ----> For example, in the case of a structure-based pharmacophore, we don't know the role of the possible induced adjustments in the conformation of the receptor binding site due to the interaction with the ligand.
Zoe Cournia, Bryce K. Allen, Thijs Beuming, David A. Pearlman, Brian K. Radak, and Woody Sherman. "Rigorous free energy simulations in virtual screening". Journal of Chemical Information and Modeling 60, no. 9 (2020): 4153-4169.
This article covers virtual screening methods including ligand-based methods and docking. It also gives a review of the thermodynamics of binding and different methods to calculate binding free energy.
[by @Daniel-Ibarrola ]