title: Automated site-directed drug design: the prediction and observation of ligand point positions at hydrogen-bonding regions on protein surfaces.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Cambridge, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Danziger
authors.forename: P M
authors.initials: PM
authors.lastname: Dean
mesh_terms: D015195:Drug Design; D006860:Hydrogen Bonding; D007256:Information Systems; D008024:Ligands; D008727:Methotrexate / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D012984:Software; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D013816:Thermodynamics; D014357:Trypsin / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D009249:NADP; D013762:Tetrahydrofolate Dehydrogenase; D014357:Trypsin; D008727:Methotrexate