The actual number and location of hydrogens in protein-ligand complexes is mutually dependent of the chemical environment induced by the respective binding partner. The tautomeric form, ionization state, and orientation of rotatable hydrogens and lone pairs influence the molecular shape and the arrangement of potential interaction sites. We present a structure-based docking approach intended for large-scale virtual screening. It automatically predicts meaningful occurrences and locations of hydrogens upon ligand placement. In this regard, the docking procedure neither requires an expansion of molecular libraries, nor efforts multiple docking runs in order to model tautomeric and protonation states of small molecules and the protein, respectively. The use of pharmacophoric constraints allows for a directed and accelerated execution, thus enabling an application in large-scale virtual screening campaigns.

Structure-based virtual screening considering multiple hydrogen interaction patterns

244th National Meeting (2012)

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