Introduction to DSX^ONLINE

1. DSX^ONLINE
2. DSX
3. Visualization
4. Acknowledgements
5. References

DSX^ONLINE

DSX^ONLINE is a web-based user interface for the knowledge-based scoring function DSX. DSX^ONLINE enables you to score (putative) protein-ligand complexes of your interest, to browse and download the scoring results, and to visualize the per-atom score contributions (see section Visualization).

DSX

DSX pair potentials are derived in analogy the the DrugScore formalism developed by Gohlke et al. [1]. However, another set of atom types is used and contact types are clustered to circumvent problems with the reference state. Torsion potentials and solvent accessible surface ratio potentials are derived using the same formalism.
For more details see the upcoming publication which is currently in preparation.
For more consistence, DSX always assigns its own atom types and hydrogens are not regarded.
If you have ligand poses from a GOLD docking where water molecules were included it is possible to consider the corresponding ON-marked waters in the solutions file.

Please note that there are even more options (like considering solutions from a docking with flexible receptor residues) available in the DSX standalone version, which will be freely available after publication.

Visualization of the per-atom score contributions

The visualization of the per-atom score contributions is an intuitive way to learn about differences between putative ligand geometries, the effects of scaffold modifications or about the importance of certain binding regions.

In the picture shown below, you find the visualization of the per-atom score contributions of thrombin (deep blue, coated by the semi-transparent molecular surface) and an in silico generated putative binding geometry of its inhibitor melagatran (green) created with PyMOL [2].
Favorably interacting atoms are surrounded by blue spheres whereas disfavorable interactions are shown in red. The sizes of the spheres correspond to the values of the contributing per-atom scores. E.g. a large blue sphere denotes a more attractive interaction than a small one, a large red sphere stands for a more repulsive interaction than a small one.



Putative complex geometry of thrombin and melagatran (click to enlarge)




Acknowledgement

We acknowledge the Cambridge Crystallographic Data Centre (CCDC) for making the CSD data available to us. We thank Dr. Hans Velec who implemented the original DrugScore-Online web pages and whose PhP- and Python-Scripts were adapted for DSX-Online.

References

[1]	Gohlke, H.; Hendlich, M.; Klebe, G. Knowledge-based scoring-function to predict protein-ligand interactions. J. Mol. Biol. 2000, 295, 337-356.
[2]	DeLano, W.L. The PyMOL Molecular Graphics System, DeLano Scientific, San Carlos, CA, USA 2002.