It has been estimated that the number of molecules with 30 atoms that can be constructed from carbon, oxygen, nitrogen, and sulfur is in excess of 10e60 . The daunting challenge of the medicinal chemist is to select from this enormous number of possibilities those molecules that willl most likely lead to the discovery of a new drug. If the three dimensional structure of the biological target is known, then the job is somewhat easier. However, the question remains how many different molecules can fit into the target binding site? And, which of all of these should be synthesized? Intrigued by these questions, we developed a computer program called GrowMol, which generates organic structures that are both spatially and chemically complementary to a target binding site. By ‘growing’ molecules an atom at a time to fill the various nooks and crannies of a binding site, GrowMol can generate structures of exquisite complementary to the host. Application to thermolysin, demonstrated that GrowMol could generate known inhibitors of thermolysin as well as large number of novel, diverse structures complementary to the thermolysin binding site . Recently Professor Daniel Rich at the University of Wisconsin has reported the use of the GrowMol program resulting with the design and synthesis of novel, potent low molecular weight inhibitors of pepsin .
Journal: TechConnect Briefs
Volume: Technical Proceedings of the 1999 International Conference on Modeling and Simulation of Microsystems
Published: April 19, 1999
Pages: 35 - 37
Industry sector: Medical & Biotech
Topics: Biomaterials, Informatics, Modeling & Simulation