Small molecule conformational preferences derived from crystal structure data. A medicinal chemistry focused analysis

J Chem Inf Model. 2008 Jan;48(1):1-24. doi: 10.1021/ci7002494. Epub 2008 Jan 10.


Based on torsion angle distributions of frequently occurring substructures, conformation preferences of druglike molecules are presented, accompanied by a review of the relevant literature. First, the relevance of the Cambridge Structural Database (CSD) for drug design is demonstrated by comparing substructures present in compounds entering clinical trials with those found in the CSD and protein-bound ligands in the Protein Data Bank (PDB). Next, we briefly highlight preferred conformations of elementary acyclic systems, followed by a discussion of sulfonamide conformations. Due to their central role in medicinal chemistry, we discuss properties of aryl ring substituents in depth, including biaryl systems and systems of two aryl rings connected by two acyclic bonds. For a subset of torsion motifs, we also compare torsion angle histograms derived from CSD structures with those derived from ligands in the PDB. Furthermore, selected properties of some six- and seven-membered ring systems are discussed. The article closes with a section on attractive sulfur-oxygen contacts.

Publication types

  • Review

MeSH terms

  • Chemistry, Pharmaceutical*
  • Crystallography, X-Ray
  • Databases, Protein
  • Drug Design
  • Molecular Conformation
  • Small Molecule Libraries*


  • Small Molecule Libraries