Structure and dynamics dictate the functional destiny of genomic DNA across multiple organisms

DNA is a dynamic molecule composed of numerous genic and regulatory elements that orchestrate cellular functions. Traditional methods often fail to provide accurate functional genome annotations because they do not effectively account for sequence variability within and across different organisms. To address this, we conducted an extensive genomic physical fingerprinting of ∼4.6 million genomic elements. Utilizing multi-microsecond molecular dynamics simulation-derived parameters over higher nucleotide steps, we uncovered critical details about the physicochemical profiles of key DNA elements, including Coding Sequences, Promoters, Gene boundaries, Exon-Intron boundaries, Start Codons, and Stop Codons across the four diverse eukaryotic kingdoms. This exploration marks a significant advancement in functional genomics and opens new avenues for genome annotation, enhancing our understanding of eukaryotic genome complexity. We identified characteristic biophysical signals associated with key genomic sites across all 11 organisms studied. Our results demonstrate that closely related organisms exhibit similar patterns, underscoring the universality of our features. Furthermore, an investigation in human Enhancers and 5'/3' UTR boundaries support this novel structural and energetic framework to annotate genomic elements with unprecedented accuracy. Lastly, sequence to structure and dynamics to function was an established axiom in proteomics. Our results demonstrate that this is true for nucleic acids as well.