Objective

To dock CombiUgi Library 3 (71K) against falcipain-2 using Fred. All of the compounds in this library have starting materials in abundance in the Bradley lab. See D-EXP012 for a similar docking run.

Procedure

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 and individual scores for each of the scoring schemes that was considered for the runs with the two binding sites named V1 and V2 (described in procedure)

DEXP014-V1A 56404 docked compounds in the V1 pocket of falcipain-2
DEXP014-V1B The first 1637 compounds of the above file. (Google Spreadsheet-shared file)

DEXP014-V2A 59402 docked compounds in the V2 pocket of falcipain-2
DEXP014-V2B The first 1500 compounds of the above file. (Google Spreadsheet-shared file)

Discussion


Conclusion