Insights into DNA solvation found in protein-DNA structures

The proteins that bind double-helical DNA present various microenvironments that sense and/or induce signals in the genetic material. The high-resolution structures of protein-DNA complexes reveal the nature of both the microenvironments and the conformational responses in DNA and protein. Complex networks of interactions within the structures somehow tie the protein and DNA together and induce the observed spatial forms. Here we show how the cumulative buildup of amino acid atoms around the sugars, phosphates, and bases in different protein-DNA complexes produces a binding cloud around the double helix and how different types of atoms fill that cloud. Rather than focusing on the principles of molecular binding and recognition suggested by the arrangements of amino acids and nucleotides in the macromolecular complexes, we consider the proteins in contact with DNA as organized solvents. We describe differences in the mix of atoms that come in closest contact with DNA, subtle sequence-dependent features in the microenvironment of the sugar-phosphate backbone, a direct link between the localized buildup of ionic species and the electrostatic potential surfaces of the DNA bases, and sites of atomic buildup above and below the basepair planes that transmit the unique features of the base environments along the chain backbone. The inferences about solvation that can be drawn from the survey provide new stimuli for improvement of nucleic acid force fields and fresh ideas for exploration of the properties of DNA in solution.