Relation of 2D and 3D descriptors of HIV protease inhibitors to drug resistance

Poster number: 31

F.Cordes (1), A. Exner (1), H. Meyer (1), D. Baum (1), M. Weber (1), J. Selbig (2)

  1. Zuse Institut Berlin (ZIB)
  2. University of Potsdam and Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm

Successful drugs against HIV have to be inhibitors against one of the virus proteins as well as its mutated variants. The process of drug development should be able to classify within an early stage new drugs according to their resistance answer of the virus.

Experimentally measured patterns of resistance factors for HIV protease inhibitors have been compared against each other according to the Euclidean, correlation coefficient-, and mutual information-based distance measure. The comparison has been used to extract a score for the structural alignment of the inhibitors. The structural score has been analyzed with respect to 2D similarity measures of topological fingerprints.

It could be shown that only the structural comparison of molecules can discriminate between inhibitors and non-inhibitors. A classification according to measured resistance patterns could be improved if the structural scoring resolves not only similar scaffolds of the inhibitors but also flexible parts which are responsible for binding characteristics.