OpenEye Scientific Software
3600 Cerrillos Rd.
Suite 1107
Santa Fe, NM, 87507
Website: http://www.eyesopen.com
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Lead Optimization Program
WABE 1.3 lead optimization program generates analogs with the same shape but more desirable electrostatics. WABE is useful for exploring the chemical space around a lead compound to elucidate candidates with improved drug profiles or novel scaffolds to avoid patent coverage. WABE generates large numbers of isosteric analogs to a lead molecule, using a graph-invariant replacement algorithm. The method resembles the process of chemical substitution, e.g. carboxylate to amide or amidine, used in medicinal chemistry to create sets of molecules having the same physical shape but varying in electrostatics. WABE then scores the analogs by electrostatic similarity to a known binder or by protein-ligand binding. The similarities between analogs eliminate computationally demanding terms, so WABE efficiently scores over 10,000 analogs per second. WABE learns the allowed atom-replacements from a user-specified training set of compounds, so it can avoid undesirable functional groups and generate chemistries suitable to a particular project. WABE can also constrain the atom replacement to certain parts of the lead molecule, which is quite useful when elaborating structure activity relationship (SAR).
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