Crowding effect on DNA melting: a molecular thermodynamic model with explicit solvent

Abstract

A molecular thermodynamic model is developed to examine crowding effect on DNA melting. Each pair of nucleotides in double-stranded DNA and each nucleotide in single-stranded DNA are represented by two types of charged Lennard-Jones segments, respectively. Water molecules are mimicked explicitly as spherical particles, embedded in a dielectric continuum. Crowders with varying concentration, size, interaction strength, and chain length are considered. For DNA with a sequence of A(20), the melting temperature is predicted to increase by 1 K in the presence of Ficoll70 and by 7.5 K in the presence of Ficoll70-polyvinyl pyrrolidone360 mixture. The predictions agree well with experimental data. Furthermore, the melting temperature is found to increase with increasing crowder size, but reduce with increasing interaction strength and crowder length. The predicted changes of Gibbs energy, entropy and enthalpy are consistent with experimentally measured values. The study reveals that DNA melting in a crowded environment is influenced by both entropic and enthalpic effects.