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).