A DNA intercalation methodology for an efficient prediction of ligand binding pose and energetics.

Motivation: Drug intercalation is an important strategy for DNA inhibition which is often employed in cancer chemotherapy. Despite its high significance, the field is characterized by limited success in identification of novel intercalator molecules and lack of automated and dedicated drug-DNA intercalation methodology. Results: We report here a novel intercalation methodology (christened 'Intercalate') for predicting both the structures and energetics of DNA-intercalator complexes, covering the processes of DNA unwinding and (non-covalent) binding. Given a DNA sequence and intercalation site information, Intercalate generates the 3D structure of DNA, creates the intercalation site, performs docking at the intercalation site and evaluates DNA-intercalator binding energy in an automated way. The structures and energetics of the DNA-intercalator complexes produced by Intercalate methodology are seen to be in good agreement with experiment. The dedicated attempt made in developing a drug-DNA intercalation methodology (compatible with its mechanism) with high accuracy should prove useful in the discovery of potential intercalators for their use as anticancers, antibacterials or antivirals. Supplementary information: Supplementary data are available at Bioinformatics online.