Applications of LUDI

In a validation study, we successfuUy applied LUDI to the design of inhibitors of dihydrofolate reductase and HIV-protease [56]. Pisabarro et al. [62] used a combination of GRID and LUDI to successfully design novel inhibitors of human synovial fluid phospholipase A2 with enhanced activity. A calculation with GRID pointed to a lipophilic binding pocket not occupied by the lead compound. LUDI was then used to search for suitable substituents to fill this pocket. One suggestion from LUDI was synthesized and found to yield a ten-fold improvement in binding affinity. 

Recently, Babine et al. used LUDI to design novel ligands for the FKBP-12 [70]. Starting from the known 3D structure of the protein, compound 3 was designed in a step-wise fash- 

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Another example of a very successful application of LUDI for designing new LAP inhibitors was discovery of phosphinate dipeptide analogues, representing a new class... 

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