Towards an Integrated Description of Hydrogen Bonding and Dehydration: Decreasing False Positives in Virtual Screening with the HYDE Scoring Function

• DOI: 10.1002/cmdc.200700319
• Publication Date: 2008-04-02T17:28:56Z
• Authors: Ingo Reulecke; Gudrun Lange; Jürgen Albrecht; Robert Klein; Matthias Rarey
• Keywords: Bond energy

We developed a new empirical scoring function, HYDE, for the evaluation of protein-ligand complexes. HYDE estimates binding free energy based on two terms dehydration and hydrogen bonding only. The essential feature this function is integrated use log P-derived atomic increments prediction energy. Taking atoms within interface into account shows that some contribute favorably to overall score, while others unfavorably. For instance, bond functions are penalized if they dehydrated unless can overcompensate loss by forming with excellent geometry. main stabilizing contribution represents removal apolar groups from water: hydrophobic effect. Initial studies using DUD dataset show there significant decrease in false positives, reasonable categorization compounds as either non-binders, weak, medium or strong binders, particular, generally applicable thermodynamically sensible cutoff score below which high likelihood compound indeed binder.