DNA SEQUENCE-DEPENDENT DEFORMABILITY DEDUCED FROM PROTEIN-DNA CRYSTALCOMPLEXES

The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening dur ing biochemically important processes. Here, a complete set of sequenc e-dependent empirical energy functions suitable for describing such be havior is extracted from the fluctuations and correlations of structur al parameters in DNA-protein crystal complexes. These elastic function s provide useful stereochemical measures of the local base step moveme nts operative in sequence-specific recognition and protein-induced def ormations. In particular, the pyrimidine-purine dimers stand out as th e most variable steps in the DNA-protein complexes, apparently acting as flexible ''hinges'' fitting the duplex to the protein surface. In a ddition to the angular parameters widely used to describe DNA deformat ions (i,e,, the bend and twist angles), the translational parameters d escribing 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 nucleo somes and other nucleoprotein complexes. The knowledge-based energies also offer realistic three-dimensional models for the study of long DN A polymers at the global level, incorporating structural features beyo nd the scope of conventional elastic rod treatments and adding a new d imension to literal analyses of genomic sequences.