Essential ingredients for rational drug design

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126674. doi: 10.1016/j.bmcl.2019.126674. Epub 2019 Sep 6.


This short review focuses on three aspects of rational drug design that we consider of utmost importance: the conformation of small molecules in solid form, the conformation of small molecules in solution and lesser studied interactions in protein-ligand complexes. Using examples from recent literature, we will illustrate these different aspects and how they have contributed to the discovery of potent modulators.

Keywords: CSD; Conformation; Dipole-dipole interaction; Dunitz interaction; NMR.

Publication types

  • Review

MeSH terms

  • Crystallography, X-Ray
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Binding


  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Ligands
  • Cyclin-Dependent Kinases