Limitations of interactive drug design: Can de novo programs fill the gap?


Regine S. Bohacek, Boston De Novo Design, 50 Commonwealth Ave. #702, Boston, MA 02116
When designing new molecules to fit a target binding site, it is easy to see where hydrophobic or hydrogen bonding ligand atoms should lie. However, it is often very difficult to find a chemical fragment that will place all these atoms into optimal positions. To be successful, a de novo program should have a rich repertoire of diverse motifs generated rapidly and with accurate geometry. The de novo program, AlleGrow (1), has achieved these goals and has been shown to generate ligands with geometries similar to those found in x-ray structures. Because AlleGrow lacked the ability to create the large number of polycyclic structures found in many drugs, a library of ~5000 heterocycles has been added. AlleGrow explorations of the binding sites of thermolysin, Src SH2 and CDK2 will be reported.

(1) AlleGrow is a second generation program based on GrowMol (R.S. Bohacek, C. McMartin, JACS (1994) 116, 5565571).


Docking and Scoring
1:30 PM-4:20 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004