Molecular Thermodynamic Model for DNA Melting in Ionic and Crowded Solutions

A molecular thermodynamic model is developed to predict DNA melting in ionic and crowded solutions. Each pair of nucleotides in the double-stranded DNA and each nucleotide in the single-stranded DNA are respectively represented by two types of charged Lennard-Jones spheres. The predicted melting curves and melting temperatures T-m of the model capture the general feature of DNA melting and match fairly well with the available simulation and experimental results. It is found that the melting curve is steeper and T-m is higher for DNA with a longer chain. With increasing the fraction of the complementary cytosine-guanine (CG) base pairs, T-m increases almost linearly as a consequence of the stronger hydrogen bonding of the CG base pair than that of adenine-thymine (AT) base pair. At a greater ionic concentration, T-m is higher due to the shielding effect of counterions on DNA strands. It is observed that T-m increases in the presence of crowder because the crowder molecules occupy a substantial amount of system volume and suppress the entropy increase for DNA melting. At a given concentration, a larger crowder exhibits a greater suppression for DNA melting and hence a higher T-m. At the same packing fraction, however, a smaller crowder leads to a higher T-m.