Thermodynamics of DNA structures under molecular crowding conditions with neutral and positive charged cosolutes

Abstract

The condition in a living cell is molecularly crowded with various biomolecules. Especially, in cell nucleus, there are high concentrations of histone proteins around DNA. Here, we analyzed quantitatively the effects of cosolutes inducing molecular crowding and histone-mimicking peptides on the thermodynamics of DNA structural formation via Watson Crick or Hoogsteen base pairs. The free energy changes for DNA structure formations with Hoogsteen and Watson-Crick base pairs decreased and increased when the concentration of poly(ethylene glycol) 200 was increased from 0 to 40 wt%, respectively. Moreover, it was observed that a histone-mimicking peptide, which is a part of the binding site of histone H3, stabilized DNA structures only with Hoogsteen base pairs. These results show that a cell nucleus mimicking condition such as a molecular crowding condition in the presence of histone proteins, stabilize DNA structures containing Hoogsteen base pairs and destabilize those with Watson-Crick base pairs, leading to structural polymorphism of various DNA sequences under molecular crowding conditions that mimic those found in cell nucleus.