DNA/RNA-drug binding studies
Therapeutic molecules that contain transition metals like Co, Ni, Cu and Zn are gaining interest as part of therapeutic drugs. These compounds interact directly with nucleic acids in different configurations such as intercalation, groove binders or stacking. Using computational tools that include Molecular Dynamics, Quantum Chemistry and Quantum Theory of Atoms in Molecules we study the specific interactions of drug-DNA complexes.
Of special interest is the binding mode known as base-pair eversion, which consist of a ligand of planar structure and with aromatic rings, binds through the minor groove of DNA and pushing an AT or GC pair, breaking the Watson-Crick pairing of the nucleotides and pushing both bases toward the major groove, flipping the bases. This results in the ligand inserting into the DNA in the resulting cavity.
DNA-protein interactions of SNPs
In this post genomic era when the human genome can be sequenced in a matter of days, our research is now focused on the functional significance of single nucleotide polymorphisms (SNPs) and their association with human diseases, giving rise to the concept of personalized medicine. When these SNPs are found in coding regions of the gene the pathway to discovery is relatively straightforward. Two recently identified SNP variations of the human genome: rs10846744 and rs73415457 have been directly linked with an increase in cardiovascular disease (CVD).
Genomic wide analysis have provided information of the importance of the Nuclear Receptor Subfamily 2, Group F, Member 2 transcription factor (NR2F2). The goal is the formation of the complex of the NR2F2 TF with the SNP sequences that have been found to increase CVD and study what the DNA sequence difference is affecting the binding with the specific TF. Since there is no experimental structure available of the TF-DNA complex, a series of homology studies, docking, molecular dynamics and quantum mechanics simulations are being performed to build a reasonable structure.
Nucleic acids dynamics
The dynamic properties and the normal “breathing” modes of nucleic acids are deeply involved in molecular recognition processes. I am interested in studying these properties of nucleic acids as a mean to understand the molecular recognition system inside the cell and how enzymes that repair DNA damage are able to quickly locate and identify mismatches, bulges, oxidation or similar type of molecular errors.
Using computational chemistry tools and spectroscopic tools, we are interested in the time-range and the modes of motion of non-canonical structures such as those present in damaged DNA.