|Dombrink Kurtzman, Mary Ann|
Submitted to: Gordon Research Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: June 29, 2001
Publication Date: N/A
Technical Abstract: Molecular dynamics methodology was used to determine the solution conformational properties of the mycotoxin fumonisin B1. Fumonisins, specifically because of their ability to inhibit sphinganine (sphingosine) N-acyltransferase (ceramide synthase), have been responsible for various toxic effects in animals. For the computational method, a box with periodic boundaries was filled with explicit TIP3P water molecules, the substrate fumonisin B1, and selected counterions for charge neutrality. The starting structure of fumonisin B1 was added to the box by excluding water molecules. Molecular dynamics were carried out on different starting conformations at 300 K in 100-picosecond steps. The resulting equilibrated conformations suggest that fumonisin B1 has a relatively extended solution structure, in contrast to previous in vacuo reports showing a compact folded structure. The molecular dynamics simulations of fumonisin B1 are in good agreement with NMR data of Blackwell and provide the structural models necessary for understanding the binding and activity properties of fumonisin B1.