The study DNA intercalating agents have gained importance in recent years due to their role in treating both parasitic and genetic diseases. Among the parasitic diseases, malaria, cause by the plasmodium falciparum, is one of the most relevant ones. In recent times, the plasmodium falciparum has become increasingly resistant to conventional drugs and the search for new agents has gained in significance.One such intercalating agent is Cryptolepine, an antimalarial drug that has potent in vitro activity against the Plasmodium Falciparum. Recent studies show that Cryptolepine interacts tightly between DNA bases pairs containing non-alternating CG sites, behaving as a typical intercalating agent. Dispersion interactions are tough to be the main component that contributes to the stability of the intercalator-DNA complex. Such interactions can be described using traditional ab-initio methods such as MP2 or highly correlated ones as CCSD(T) at a high computational cost. Popular conventional density functional theory (DFT), unfortunately, fails completely do describe dispersion interactions even qualitatively. We propose to investigate using first principles methodologies the nature of criptolepin-DNA complex by using DFT augmented with dispersion corrected atom centered potentials (DCACP) for the correct description of dispersion interactions. The effects of the medium, solvent and protein, will be treated with a hybrid QM/MM approach. Criptolepin is one of the few intercalating agents, and the only anti-malaria drug, that bind preferentially to non-alternating CG sites. We believe that, by describing the details of the intercalation process, we can help with the design of new anti-malaria drugs.
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