Docking small ligands in flexible binding sites

: A novel procedure for docking ligands in a flexible binding site is presented. It relies on conjugate gradient minimization, during which nonbonded interactions are gradually switched on. Short Monte Carlo minimization runs are performed on the most promising candidates. Solvation is implicitly taken into account in the evaluation of structures with a continuum model. It is shown that the method is very accurate and can model induced fit in the ligand and the binding site. The docking procedure has been successfully applied to three systems. The first two are the binding of progesterone and 5␤-androstane-3,17-dione to the antigen binding fragment of a steroid binding antibody. A comparison of the crystal structures of the free and the two complexed forms reveals that any attempt to model binding must take protein rearrangements into account. Furthermore, the two ligands bind in two different orientations, posing an additional challenge. The third test case is the docking of ␣ Ž ...

• Type: Journal
• Year: 1998
• Where: JCC
• Authors: Joannis Apostolakis, Andreas Plückthun, Amedeo Caflisch
• Keywords: Binding Site, Flexible Binding Site, JCC 1998, Ligand