Development of a Novel Method for Representing 3D Structures of Nucleotides Using the Concept of the TSR Algorithm and Evaluation of the Method Through Studying Specific Interactions Between DNAs and p53.

Prior evidence has suggested that interactions between transcription factor amino acids and DNA nucleotides follow a recognition code. However, the recognition code remains poorly understood due to the inability of currently available computational methods to quantify and interpret subtle conformational changes of transcription factor amino acids and DNA nucleotides. In this study, we have developed a novel way of representing 3D structures of nucleotides of DNAs or RNAs by adapting the concept of the Triangular Spatial Relationship (TSR) from the TSR-based computational method originally designed for protein 3D structural comparisons. Representing nucleotide 3D structures using a vector of integers (TSR keys) is unique. We chose p53 as an example of a transcription factor to establish the structural basis for comprehending the recognition code. By taking advantage of the proposed representation of nucleotide 3D structures, we were able to demonstrate the structural differences between the nucleotides that interact with p53 and those that do not interact with p53 as well as the structural differences between the amino acids of p53 that interact with DNA and those that do not interact with DNA. In summary, this study demonstrates the capabilities of an advanced computational methodology with notable advantages for representing and quantifying nucleotide structures and for providing a comprehensive understanding of the structural specificity existing between p53 proteins and their binding DNAs. Such an analysis can also be extended to complexes involving other transcription factor-DNA pairs.