Control of DNA minor groove width and Fis protein binding by the purine 2-amino group.

The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis-DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis-DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes

Protonation State-Dependent Communication in Cytochrome c Oxidase

Proton transfer in cytochrome c oxidase from the cellular inside to the binuclear redox center (BNC) can occur through two distinct pathways, the D- and K-channels. For the protein to function as both a redox enzyme and a proton pump, proton transfer into the protein toward the BNC or toward a proton loading site (and ultimately through the membrane) must be highly regulated. The PR → F transition is the first step in a catalytic cycle that requires proton transfer from the bulk at the N-side to the BNC. Molecular dynamics simulations of the PR → F intermediate of this transition, with 16 different combinations of protonation states of key residues in the D- and K-channel, show the impact of the K-channel on the D-channel to be protonation-state dependent. Strength as well as means of communication, correlations in positions, or communication along the hydrogen-bonded network depends on the protonation state of the K-channel residue K362. The conformational and hydrogen-bond dynamics of the D-channel residue N139 is regulated by an interplay of protonation in the D-channel and K362. N139 thus assumes a gating function by which proton passage through the D-channel toward E286 is likely facilitated for states with protonated K362 and unprotonated E286. In contrast, proton passage through the D-channel is hindered by N139’s preference for a closed conformation in situations with protonated E286

Optical properties of triplex DNA from time-dependent density functional theory

We present a combined investigation of the dynamics and optics of triplex DNA, based on classical molecular dynamics and time-dependent density functional theory. Our approach is devised to include the effects of conformational fluctuations on the electronic structure and optical excitations of the system. We find that the structural flexibility has a strong role in the determination of the optical signals. Our results allow us to unravel the peculiar fingerprints of Watson-Crick and Hoogsteen H-bonding in the optical absorption spectra. We find a specific optical absorption feature that is due to the simultaneous presence of the two H-bonding patterns in C+GC triplets. While this peculiar triplet signal is wiped out in some structures that are representative of the finite-temperature dynamics, it can be recovered in an average view, so that it is a pristine result of this work. © 2012 American Chemical Society

Control of DNA minor groove width and Fis protein binding by the purine 2-amino group.

The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis-DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis-DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes

Control of DNA minor groove width and Fis protein binding by the purine 2-amino group

The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis–DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis–DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes