De Novo Design of Enzyme Inhibitors by Monte Carlo Ligand Generation
Daniel K. Gehlhaar, Karl E. Moerder, Dominic A. Zichi, Christopher J. Sherman, Richard C. Ogden, Stephan T. Freer · Journal of Medicinal Chemistry · 1995
A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease. One such improvement resulted in a compound selected for preclinical studies as an antiviral agent against AIDS.