Docking of flexible ligands to flexible receptors in solution by moleculardynamics simulation

In this paper, a method of simulating the docking of small flexible ligands to flexible receptors in water is reported. The method is based on molecul ar dynamics simulations and is an extension of an algorithm previously repo rted by Di Nola et al, (Di Nola et al,, Proteins 1994;19:174-182), The meth od allows a fast exploration of the receptor surface, using a high temperat ure of the center of mass translational motion, while the ligand internal m otions, the solvent, and the receptor are simulated at room temperature. In addition, the method allows a fast center of mass motion of the ligand, ev en in solution. The dampening effect of the solvent can be overcome by appl ying different weights to the interactions between system subsets (solvent, receptor, and ligand), Specific ligand-receptor distances have been used t o compare the results of the simulations with the crystal structure. The me thod is applied, as a test system, to the docking of the phosphocholine to the immunoglobulin McPC603. The results show the similarity of structure be tween the complex in solution and in the crystal. (C) 1999 Wiley-Liss, Inc.