Effects of Mg²⁺ on the binding of the CREB/CRE complex: Full-atom molecular dynamics simulations

Metal ions play critical roles in the interaction between deoxyribonucleic acid (DNA) and protein. The experimental research has demonstrated that the Mg²⁺ ion can affect the binding between transcription factor and DNA. In our work, by full-atom molecular dynamic simulation, the effects of the Mg²⁺ ion on the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB)/cAMP response elements (CRE) complex are investigated. It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg²⁺ ion is added. Hence, an obvious change in the structure of the DNA is observed. Then the DNA base groove and base pair parameters are analyzed. We find that, due to the introduction of the Mg²⁺ ion, the DNA base major groove becomes narrower. A potential mechanism for this observation is proposed. It is confirmed that the Mg²⁺ ion can enhance the stability of the DNA–protein complex. (paper)