Docking of flexible ligands to flexible receptors in solution by molecular dynamics simulation
Mangoni R, Roccatano D, Di Nola A
PROTEINS-STRUCTURE FUNCTION AND GENETICS
35 (2): 153-162 MAY 1 1999

FULL TEXT

Abstract:

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 molecular dynamics simulations and is an extension of an algorithm previously reported by Di Nola et al, (Di Nola et al,, Proteins 1994;19:174-182), The method allows a fast exploration of the receptor surface, using a high temperature of the center of mass translational motion, while the ligand internal motions, the solvent, and the receptor are simulated at room temperature. In addition, the method allows a fast center of mass motion of the ligand, even in solution. The dampening effect of the solvent can be overcome by applying different weights to the interactions between system subsets (solvent, receptor, and ligand), Specific ligand-receptor distances have been used to compare the results of the simulations with the crystal structure. The method is applied, as a test system, to the docking of the phosphocholine to the immunoglobulin McPC603. The results show the similarity of structure between the complex in solution and in the crystal.

Author Keywords:

docking, molecular dynamics, rational drug design, immunoglobulin

KeyWords Plus:

AUTOMATED DOCKING, 3-DIMENSIONAL STRUCTURE, GENETIC ALGORITHM, PROTEIN DOCKING, BINDING-SITES, FREE-ENERGY, COMPLEMENTARITY, RECOGNITION, COMPLEXES

Addresses:

Di Nola A, Univ Rome La Sapienza, Dept Chem, POB 34 Roma 62,Piazzale Aldo Moro 5, I-00185 Rome, Italy
Univ Rome La Sapienza, Dept Chem, I-00185 Rome, Italy
Univ Groningen, Dept Biophys, NL-9700 AB Nijenborgh, Netherlands