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Post-docking virtual screening of diverse binding pockets: comparative study using DOCK, AMMOS, X-Score and FRED
Tania Pencheva1, Oumarou Samna Soumana, Ilza Pajeva
1Centre of Biomedical Engineering, Bulgarian Academy of Sciences, 105 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria. tania.pencheva@clbme.bas.bg
European Journal of Medicinal Chemistry
|March 16, 2010
Summary
No single docking scoring function excels across all protein targets. Empirical scoring functions suit hydrophobic pockets, while force field methods perform better on mixed or polar binding sites.
Area of Science:
- Computational chemistry
- Molecular modeling
- Drug discovery
Background:
- No single scoring function consistently performs well across diverse protein targets.
- Scoring functions are crucial for predicting ligand-protein binding affinity in drug discovery.
Purpose of the Study:
- To compare the performance of thirteen common force field and empirical scoring functions.
- To analyze scoring function performance based on binding site physicochemical properties.
- To evaluate the ability of scoring functions to discriminate active from inactive compounds.
Main Methods:
- Comparison of thirteen scoring functions (DOCK, AMMOS, X-Score, FRED) across five diverse protein targets.
- Analysis of scoring function performance correlated with binding site properties.
- Inclusion of Generalized Born/Surface Area (GBSA) solvation for one scoring function.
- Evaluation using receptor-based focused libraries to assess active/inactive discrimination.
Main Results:
- Empirical scoring functions showed better performance on hydrophobic binding pockets.
- Force field scoring functions demonstrated superior performance on mixed or polar binding pockets.
- Performance varied significantly depending on the specific protein target and binding site characteristics.
Conclusions:
- The choice of scoring function should be tailored to the specific physicochemical properties of the target binding site.
- Understanding binding site characteristics is critical for selecting appropriate docking-scoring methods.
- Further development of scoring functions considering solvation effects and diverse binding site properties is warranted.
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