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Keywords:

  • protein–ligand complex;
  • binding pocket ensemble;
  • pocketome;
  • virtual ligand screening;
  • binding energy prediction

Abstract

The rapid growth of the available crystallographic information about proteins and binding pockets creates remarkable opportunities for enriching the drug research pipelines with computational prediction of novel protein–ligand interactions. While ab initio quantum mechanical (QM) approaches are known to provide unprecedented accuracy in structure-based binding energy calculations, they are limited to only small systems of dozens of atoms. In the structural chemogenomics era, it is critical that new approaches are developed that enable application of QM methodologies to noncovalent interactions in systems as large as protein–ligand complexes and conformational ensembles. This perspective highlights recent advances towards bridging the gap between high-accuracy and high-volume computations in drug research. © 2013 Wiley Periodicals, Inc.