To perform docking in Makya, users can choose between the following softwares:
- Autodock Vina, whose scoring function is referred to as the Vina Score
- rDock, whose scoring function is referred to as the SCORE STANDARD
The generated molecules are docked in the specified target protein binding pocket and optimized with respect to the Contact Score and the scoring function of the selected software.
Which docking tool should I use?
We recommend using rDock for fast, cheaper and generally more accurate docking.
When generations with rDock return unsatisfactory results in terms of docking pose and ranking power, we recommend trying Vina with a medium exhaustiveness level.
Comparison of the Scoring Functions
In the table below, we give a brief overview of the main differences between the available scoring functions; for more details, the reader is invited to refer to the original Autodock Vina paper [1] and rDock paper [2].
| Vina Score (Vina) | SCORE STANDARD (rDock) | |
| Scoring Function | Empirical (weighted terms including van der Waals, hydrogen bonding, and hydrophobic effects). | Knowledge- and physics-based, combining steric, electrostatic, and solvation terms. |
| Search Algorithm | Iterative global-local optimization using a genetic algorithm-inspired heuristic. | Uses 3 stages of Genetic Algorithm search (GA1, GA2, GA3), followed by low temperature Monte Carlo (MC) and Simplex minimization (MIN) stages. |
| Accuracy | Reasonably accurate, but limited by simplified scoring functions. | Good accuracy for protein-ligand systems |
| Configurability | Limited configurability; scoring and parameters are predefined and optimized for speed. | Highly configurable; allows custom scoring functions and docking protocols. |
| Special Features |
- Efficient for high-throughput docking. - User-friendly. |
- Highly flexible for custom docking protocols. - Pharmacophoric restraints - Tethered template restraint - Water molecule flexibility and occupancy |
| Receptor Flexibility | Limited; receptor is mostly rigid. | Allows for limited receptor flexibility. |
| Ligand Flexibility | Fully flexible ligands (rotatable bonds considered). | Fully flexible ligands with added custom flexibility options. |
| Input/Output Formats |
Input: PDBQT. Output: PDBQT and binding affinities. |
Input: Mol2, SDF, or PDB. Output: Docked structures with detailed scores. |
| Use Cases | Small-molecule docking in protein targets; drug screening. | Docking in protein-ligand systems; advanced docking with restraints. |
| Strengths |
- Fast and reliable. - Great for large-scale virtual screening. |
- Highly customizable for specific use cases. - Fast docking. |
| Weaknesses |
- Limited flexibility for advanced docking protocols. - Scoring function may lack accuracy for complex systems. |
- Complex to set up. - Hard to play with the expert parameters. |
References
-
Trott O, Olson AJ (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31 455-461. https://doi.org/10.1002/jcc.21334
- Ruiz-Carmona S, Alvarez-Garcia D, Foloppe N, Garmendia-Doval AB, Juhos S, Schmidtke P, et al. (2014). rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids. PLoS Comput Biol 10(4): e1003571. https://doi.org/10.1371/journal.pcbi.1003571