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. J Comput Chem 24: 682–691, 2003