D-EXP012

=Objective= To dock CombiUgi Library 2 (500K) against falcipain-2 using Fred. =Procedure= Full explanation given by [|Rajarshi Guha]

The target of interest is the falcipain-2 enzyme. The crystal structure is available on the PDB ([|1YVB] ). This structure contains falcipain bound to cystatin and a glycerol along with some waters. The cystatin, glycerol and waters were removed for docking purposes. Since the complex is an example of a protein protein interaction, identifying the binding site was a bit tricky.

We identfied two possible regions based on visual inspection as well as predicted hot-spot residues using the SPPIDER server (get the report [|here] ). This led to two sets of docking runs (V1 and V2). The important thing to note is that I don't know for sure whether these are the correct regions for a small molecule to interact and subsequently inhibit. V2 is probably a better bet, since it seemed reasonable visually and was also in the region of the residues predicted by SPPIDER.

=Results= The rescored data files (containing the final consensus scores as well as the individual scores for each of the scoring schemes that we considered) for the runs with the two binding sites are here: [|Scores for V1] and [|Scores for V2]. The top 10 molecules from the V1 binding site are listed [|here]. The first column is the serial number of the molecule. The column titled Cons.Score is the consensus score generated by considering all docked ligands. In all columns lower numbers are better

=Discussion= [|See mailing list discussion.] =Conclusion= Two docking regions on falcipain-2 were used to dock CombiUgi library 2 and these were ranked by the docking program Fred.