Conformational stability and order of Hoogsteen base pair induced by protein binding

Several experimental studies have shown that in the presence of proteins, the Hoogsteen (HG) base pair (bp) becomes stabilized. The molecular mechanism underlying this stabilization is not well known. This leads us to use all-atom molecular dynamics simulation to examine the stability of the HG bp in duplex DNA in both the absence and presence of proteins. We use conformational thermodynamics to investigate the stability of a HG bp in duplex DNA at the molecular level. We also compute the changes in the conformational free energy and entropy of DNA when DNA adopts a HG bp in its bp sequence rather than a Watson-Crick (WC) bp in both naked DNA and protein-bound DNA complex. We observe that the HG bp and the entire DNA duplex conformation are stabilized and ordered in the presence of proteins. Sugar-phosphate, sugar-base, and sugar-pucker torsion angles play key roles in stabilizing and ordering the HG bp in the protein-bound DNA complex.