COMP 217 |
| Since family 18 chitinases are essential enzymes for fungi and insects, they are potential targets for the design of antifungals and pesticides. Recently, a novel cyclic pentapeptide chitinase inhibitor, argadin, has been isolated. The crystal structure of argadin binding to a family 18 chitinase from Serratia marcescens [ChiB] has been also reported. In this study, we design a new non-peptide chitinase inhibitor using a molecular modeling method on the basis of the interaction mode of argadin with ChiB. First, the peptide backbone of argadin is replaced by a 14-membered macrolide that possesses more drug-like properties. Then, the functional groups corresponding to the side chains of argadin are introduced to the 14-membered macrolide. The docking and free energy calculations suggest that the designed molecule could bind to ChiB in the fashion similar to argadin-ChiB interaction mode and have a binding affinity comparable to that of argadin. |
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Poster Session
6:00 PM-8:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Computers in Chemistry |