Automated site-directed drug design: the prediction and observation of ligand point positions at hydrogen-bonding regions on protein surfaces

Proc R Soc Lond B Biol Sci. 1989 Mar 22;236(1283):115-24. doi: 10.1098/rspb.1989.0016.


The HSITE program proposed in the previous paper was written to define putative ligand-point regions that could be found at protein surfaces. These regions would represent positions for hydrogen-bonding acceptor and donor atoms. In this paper the prediction of the location of these regions is compared with: (1) the position of the oxygen atoms of water molecules on the hydrated proteins myoglobin and plastocyanin; and (2) the position of hydrogen-bonded atoms in methotrexate and NADPH co-crystallized with dihydrofolate reductase, and in amidinophenyl-pyruvate co-crystallized with trypsin. The prediction of ligand-point regions is in agreement with the surveys of experimental data for water-molecule positions in protein crystals and with the positions of hydrogen-bonding atoms found in co-crystallized ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design*
  • Hydrogen Bonding
  • Information Systems
  • Ligands*
  • Methotrexate / metabolism
  • NADP / metabolism
  • Proteins / metabolism*
  • Software
  • Tetrahydrofolate Dehydrogenase / metabolism*
  • Thermodynamics
  • Trypsin / metabolism


  • Ligands
  • Proteins
  • NADP
  • Tetrahydrofolate Dehydrogenase
  • Trypsin
  • Methotrexate