In the DNA field, we have been studying short tandem repeats (STRs) that represent about 3% of the human genome and influence gene expression, recombination, and maintenance of chromatin spatial organization.
We have also extended the Alanine Scanning Mutagenesis (ASM) method previously developed by us for the application in protein-DNA interfaces. To the best of our knowledge this was the first time that such method was applied to protein-DNA due to the inherent difficulty in characterizing the energetics of these highly charged systems. We studied the influence of the variation of several parameters in the calculation of the binding free energy values for a set of protein-DNA complexes. In particular we focused our attention on the influence of: (i) the ionic concentration; (ii) the energy terms included in the calculation; (iii) various types of solvent representation; (iv) the MD simulation time; and (v) the internal dielectric constant.