Protein-DNA interactions are essential to biological processes such as DNA repair, DNA replication, gene regulation and maintenance of genome stability. There are two general types of protein-DNA interactions: proteins-dsDNA (double-stranded DNA) and protein-ssDNA (single-stranded DNA). While dsDNA consists of two complementary strands adopting a double helix structure stabilized by base pairing and base stacking interactions, ssDNA is more flexible with bases accessible for additional interactions with proteins. It has been demonstrated that hydrogen bonds play crucial roles in conferring protein-DNA binding specificity. To investigate the role of hydrogen bonds in specific protein-dsDNA and protein-ssDNA interactions, we performed comparative analyses of hydrogen bond energy between non-redundant protein-dsDNA and protein-ssDNA complexes with respect to their binding specificity. Our results indicate that there are more hydrogen bonds between protein sidechain and DNA base in specific protein-DNA complexes than those in non-specific protein-DNA complexes. About 50% of hydrogen bonds are mixed types, either between protein sidechain and DNA backbone or between DNA base and protein backbone with the former as the dominant type. Specific protein-ssDNA complexes have more sidechain-base hydrogen bonds than those in specific protein-dsDNA complexes. More importantly, in specific protein-ssDNA complexes, the hydrogen bonds are significantly stronger than those from the specific protein-dsDNA complexes and non-specific protein-DNA complexes.
Judyani et al. (Sun,) studied this question.