Binding of proteins to the minor groove of DNA: What are the structural and energetic determinants for kinking a basepair step?

The structural and energetic determinants for kinking a basepair step by minor groove-insertion of the protein side chains of PurR, LacI, LEF-1, IHF, Sac7d, and Sso7d, have been calculated by molecular dynamics/potential of mean force simulations. The structural determinants of the kinked structures are: two contiguous furanose rings achieve different conformations, in the region of C3'endo (A-DNA) and C2'endo (B-DNA); the χ torsion angle always takes values characteristic of the C2'endo conformation of B-DNA, independently of sugar puckering; and protein side chain insertion increases slide (from negative to positive values), rise, and roll, and decreases twist. The energetic determinants of DNA kinking are: the conformational transition of the sugar-phosphate backbone is not energetically demanding; the relative importance of the interbase parameters in the free energy penalty is slide, followed by twist and rise, and concluding with shift and roll; and the characteristic increase of roll and decrease of twist, upon side chain insertion, tends to stabilize the process of DNA kinking. © 2003 Wiley Periodicals, Inc.