Results
Description
In the WISDOM-I project, one million compounds were screened against 5 different plasmepsins by using two software.
- the PDB structures were obtained from Brookhaven protein database (http://www.pdb.org/),
- the chemical compounds are obtained in a ready to dock format from ZINC database (http://blaster.docking.org/zinc/),
- the first docking software used is FlexX, a commercial software from http://www.biosolveit.de/. Two different parameters for FlexX were used while screening, they are the Place particles on/off and Max Overlap volume 2.5/5.0 (FlexX user manual, Mathias Rarey),
- the second docking software is Autodock (http://autodock.scripps.edu/). Results are not presented here.
Result analysis
After several test runs, the results with FlexX software on target structure 1lee were analyzed. The primary criteria in the selecting the compounds is based on the docking score. Top 5,000 compounds from all the parameters were selected. These 5,000 compounds are manually inspected further. The further strategies to reduce the false positives include exploiting the interactions to the key residues of the protein and binding mode of the compounds.
Final Result
Finally 100 compounds have been selected. Most of the compounds selected possess thiourea, diphenyl urea and guanidino scaffolds.
