Sensitivity of an empirical affinity scoring function to changes in receptor-ligand complex conformations

A combination of empirical scoring and conformational sampling for ligand b inding affinity prediction is examined. The behaviour of a scoring function with respect to the sensitivity to conformational changes is investigated using ensembles of structures generated by molecular dynamics simulation. T he correlation between the calculated score and the coordinate deviation fr om the experimental structure is clear for the complex of arabinose with ar abinose-binding protein, which is dominated by hydrogen bond interactions, while the score calculated for the hydrophobic complex between retinol and retinol binding protein is rather insensitive to ligand conformational chan ges. For typical ensembles of stuctures generated by molecular dynamics at 300 K. the variation of the calculated score is considerably smaller than t hat of the underlying molecular mechanics interaction energies. (C) 2001 El sevier Science BY All rights reserved.