DNA sequence-dependent deformability deduced from protein–DNA crystal complexes

TLDR

DNA deformability is essential for cellular packaging, molecular recognition, transient opening, and nonplanar folding in nucleosomes, as revealed by correlations of base‑pair bending and shearing motions. The study aims to extract a complete set of sequence‑dependent empirical energy functions describing DNA deformability from fluctuations and correlations in DNA–protein crystal complexes. The authors derive energy functions by analyzing both angular (bend, twist) and translational (displacement along and across the helix) parameters from DNA–protein crystal structures. The derived elastic functions quantify local base‑step movements, highlight pyrimidine‑purine dimers as flexible hinges, and enable realistic 3D modeling of long DNA polymers beyond conventional elastic rod treatments.

Abstract

The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the fluctuations and correlations of structural parameters in DNA–protein crystal complexes. These elastic functions provide useful stereochemical measures of the local base step movements operative in sequence-specific recognition and protein-induced deformations. In particular, the pyrimidine-purine dimers stand out as the most variable steps in the DNA–protein complexes, apparently acting as flexible “hinges” fitting the duplex to the protein surface. In addition to the angular parameters widely used to describe DNA deformations (i.e., the bend and twist angles), the translational parameters describing the displacements of base pairs along and across the helical axis are analyzed. The observed correlations of base pair bending and shearing motions are important for nonplanar folding of DNA in nucleosomes and other nucleoprotein complexes. The knowledge-based energies also offer realistic three-dimensional models for the study of long DNA polymers at the global level, incorporating structural features beyond the scope of conventional elastic rod treatments and adding a new dimension to literal analyses of genomic sequences.