Epothilones: Quantitative structure activity relations studied by support vector machines and artificial neural networks

In this paper the relation between the structure of epothilones (a new class of anti-tumour agents) and their potential to influence the tubulin-microtubule equilibrium is investigated. Insights into the character of the tubulin-epothilone interactions are derived as the accuracy and reliability of support vector machines and artificial neural networks to model such relations quantitatively is compared. Both methods are well qualified to model relationships between the structure of epothilone derivatives and their anti-tumour activities. Artificial neural networks achieve lower residual standard deviations (22%) compared to support vector machines (25%) and better classification results (89% compared to 75%). However, the reproducibility of the results is greater for support vector machines, which suggests a stronger convergence. The mapping of the influence of individual structural descriptors on the three-dimensional epothilone structure suggests one side of the rather flat molecule to be more important for its activity. The "LIBSVM" software which is used for simulating the support vector machines is freely available from www.csie.ntu.edu.tw/similar tocjlin/libsvm. The Program "Smart" which is used for simulating artificial neural networks is free for academic use and can be obtained together with the database of epothilones and their activities from www.jens-meiler.de.