Hi

I am trying to calculate the binding energy of a single ligand to various mutant proteins.  The ligand has been co-crystallized with the wild-type protein and falls in the same cell as the protein in the DS hierarchy tab. 

The various mutants were created, prepared and minimized with implicit GBSW solvation.

Prior to calculating the binding energy on the minimized structure I cut and pasted the ligand into a new cell then defined the rest of the protein as receptor and the ligand (now in new cell) as ligand in the receptor-ligand interaction tab.  Input for the calculate binding energy protocol is then the receptor and all visible ligands for that molecule window.

This approach worked fine and I was able to calculate the binding energy for all structures with GBSW.  However, my in silico results did not follow the same trend as the in vitro enzyme kinetics (Ki values) which could be due to the binding being mediated by specific water molecules.  To check the effect of solvent I proceeded by solvating the prepared structure with minimization, minimization of the protein and then defining ligand, receptor and binding site as described above.  This resulted in an error! Discovery Studio does not seem to detect the ligand at all in the presence of the explicit waters and just says ''Error: 0 poses'' even though the ligand is present.  I also tried extracting the ligand to a new molecule window after minimization, saving it as sd file for ligand input but this still gave the same error.

Any thoughts on what the problem might be?

Thanks