LigBuilder: A multi-purpose program for structure-based drug design

We have developed a new multi-purpose program, LigBuilder, for structure-ba sed drug design. Within the structural constraints of the target protein, L igBuilder builds up ligands step by step using a library of organic fragmen ts. Various operations, such as growing, linking, and mutation, have been i mplemented to manipulate molecular structures. The user can choose either g rowing or linking strategies for ligand construction and a genetic algorith m is adopted to control the whole construction process. Binding affinities of the ligands are estimated by an empirical scoring function and the bioav ailabilities are evaluated by a set of chemical rules. Using thrombin and d ihydrofolate reductase as examples, we have demonstrated that LigBuilder is able to generate chemical structures similar to the known ligands.