[Molecular dynamics simulation of the tubulin dimer with cytostatics]

Colchicin, podophylotoxin and indibulin are natural cytostatics that are used in the treatment of neoplasms. But applications of those compounds are rather restricted due to the high toxicity and low specificity. It seems very promising to investigate possibility to design new analogs of the above mentioned drugs that will possess higher cytostatic activity and less toxicity. For this purpose we see computer modeling experiments of tubulin and above mentioned compounds interaction as a powerful approach to design new artificial cytostatics with desired properties. In the current study the CHARMM software of protein-ligand interaction molecular dynamics method has been used. Particularly the following strategy has been applied. Molecules of the cytostatits have been positioned at several random positions around binding sites of tubulin and after energy minimization several binding sites have been identified on the tubulin macromolecule. In these binding sites structural changes that may be responsible for tubulin polymerization have been detected.