This article is part of the supplement: 3rd German Conference on Chemoinformatics: 21. CIC-Workshop .

Poster presentation

The influence of protonation in protein-ligand docking

ten T Brink and TE Exner

Theoretische Chemische Dynamik, Fachbereich Chemie, Universität Konstanz, D-78457 Konstanz, Germany

corresponding author email

from 3rd German Conference on Chemoinformatics
Goslar, Germany. 11-13 November 2007

Chemistry Central Journal 2008, 2(Suppl 1):P12doi:10.1186/1752-153X-2-S1-P12

The electronic version of this abstract is the complete one and can be found online at: http://www.journal.chemistrycentral.com/content/2/S1/P12

Published:

26 March 2008

© 2008 Brink and Exner

Poster presentation

With the use in Virtual Screening (VS) in experiments Protein-Ligand-Docking has gained more and more importance in pharmaceutical research over the past years. To model the interactions between the protein and a ligand empirical scoring functions are used in many programs. These scoring functions consist of different terms, which describe physical and chemical properties important for an attractive interaction between the protein and the ligand. Most scoring functions use hydrogen bonds and salt bridges as descriptors. For both the knowledge of the protein's and the ligand's protonation state is important but experimental methods like x-ray crystallography do not resolve the hydrogen atom positions in protein structures.

To estimate the influence of the ligand's protonation on the docking results with PLANTS [1] and Gold [2] different protonation states of each ligand of the ASTEX clean test set [3] were automatically generated using a combinatorial method. This method adds and removes single hydrogen atoms and considers ketone-enol tautomerism on the ligand side. The number of different protonation states ranged from 1 to 64 depending on the ligand's structure. For a small number of test cases, the different protein protonation states were also generated by applying the same method to the surface atoms of the binding pockets. Docking studies for all gernerated protonation states were made using PLANTS and Gold with standard settings.

References

1. Korb O, Stützle T, Exner TE:

   LNCS. 2006 , 4150:247-258.

2. Verdonk ML, Cole JC, Hartshorn MJ, Murray CW, Taylor RD:

   Proteins. 2003 , 52:609-623. PubMed Abstract | Publisher Full Text

3. Nissink J W M, Murray C, Hartshorn C, Verdonk ML, Cole JC, Taylor R:

   Proteins. 2002 , 49(4):457-471. PubMed Abstract | Publisher Full Text

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