A Survey of DNA–Protein π–Interactions: A Comparison of Natural Occurrences and Structures, and Computationally Predicted Structures and Strengths

Abstract

Non-covalent interactions between DNA and proteins play critical roles in cellular functions, including DNA replication and repair. To gain an appreciation of the biomolecular components involved, several bioinformatics studies have data mined experimental X-ray crystal structures to identify close contacts between DNA and protein building blocks. These critical studies have revealed that DNA–protein non-covalent interactions include π–π, C–H···π, O–H···π, N–H···π or lone pair–π (X···π, X = O, N or S) contacts. Unfortunately, however, experimental structural data cannot provide information about the relative strength of biologically-relevant non-covalent interactions. Therefore, quantum mechanical calculations have been used to determine the stability of DNA–protein π–heterodimers, as well as the dependence of the interaction energy on changes in relative monomer orientations. In this light, the present review summarizes work done in the literature to characterize π–interactions between the DNA nucleobases (A, C, T and G) or deoxyribose moiety and cyclic (His, Phe, Tyr and Trp) or acyclic (Arg, Glu and Asp) amino acid side chains. Collectively, this body of work emphasizes the importance of DNA–protein π–interactions for providing stability to biomolecular complexes and driving key cellular functions.