Further Insight into the Interactions of the Cytotoxic Macrolides Laulimalide and Peloruside A with Their Common Binding Site.

ABSTRACT: The binding site of the macrolides laulimalide and peloruside A, which is different from that of the clinically useful drugs paclitaxel/taxol and ixabepilone (tax site), is known to be between two adjacent β-tubulin units (ext site). Here, we report our study of the binding of these molecules to an α1β1/α2β2-tubulin "tetramer" model. AutoDock 4.2.6//AutoDock Vina dockings predicted that the affinities of laulimalide and peloruside A for the tax site are quite similar to those for the ext site. However, molecular dynamics (MD) simulations indicated that only when these two ligands are located at the ext site, there are contacts that help stabilize the system, favoring the β1/β2 interactions. The binding affinity of laulimalide for this site is stronger tha

SUBMITTER: Castro-Alvarez A 

PROVIDER: S-EPMC6641392 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature