Effect of CpG methylation on DNA binding protein: Molecular dynamics simulations of the homeodomain PITX2 bound to the methylated DNA

► Exploring effect of CpG methylation on DNA-binding transcription factor will be useful. ► The binding-induced structural changes upon the DNA-PITX2 complexation are further encouraged by CpG methylation. ► Recognizing sites by the Lys50 appear to have distinct mobility due to CpG methylation. ► The methylated CpG that is close to the binding region between PITX2 and the DNA major groove can promote the DNA-protein association. ► CpG methylation can reduce the unfavorable entropic effects and increase the binding free energy of PITX2-DNA association.