Three-dimensional structure of a DNA hairpin in solution: two-dimensional NMR studies and distance geometry calculations on d(CGCGTTTTCGCG)

Abstract

The three-dimensional structure of d(CGCGTTTTCGCG) in solution has been determined from proton NMR data by using distance geometry methods. The rate of dipolar cross-relaxation between protons close together in space is used to calculate distances between proton pairs within 5 A of each other; these distances are used as input to a distance geometry algorithm that embeds this distance matrix in three-dimensional space. The resulting refined structures that best agree with the input distances are all very similar to each other and show that the DNA sequence forms a hairpin in solution; the bases of the loop region are stacked, and the stem region forms a right-handed helix. The advantages and limitations of the technique, as well as the computer requirements of the algorithm, are discussed.

Moving beyond Watson–Crick models of coarse grained DNA dynamics

“…The parameters δ ij k for hydrogen bonding and stacking are estimated from a range of experimental and computational data in the literature. 30,35,36,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] Since we eventually choose to match the experimental data for hairpin melting curves, 37 we only need to determine the relative strengths of each interaction. We first grouped all of the references by the type of measurement, often with several publications per group.…”

“…The values of the δ ij k parameters for Watson-Crick and Hoogsteen hydrogen bonds 30,35,36,[47][48][49][50][53][54][55][56] are listed in Table I. For hydrogen bonding, we do not allow any bonds between base i and i + 2 on the same strand to avoid the formation of one member loops.…”

Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

“…DG-BKCALC method. The DG algorithm DSPACE and the BKCALC program have been described previously (Hare and Reid, 1986;Banks et al, 1989;Metzler et al, 1989;Summers et al, 1990). Out of at least 30 random trial structures, 6-10 low-penalty structures (penalty = sum of the squared differences between interatomic distances in the structure and the bounds matrix) were generated (total penalty c 0 .…”

“…angle constraints derived from NMR data: d(CGCGT,CGCG) (Hare and Reid, 1986), d(ATCCTAT,TAGGAT) (Blommers et al, 1987) and d(CGATCGT,CGATCG) (Baxter et al, 1993). The Hare model was derived by distance geometry (DG), the Blommers model by molecular modeling (MM), and the Baxter model by molecular dynamics (MD) and MM.…”

Simulated annealing with restrained molecular dynamics using a flexible restraint potential: Theory and evaluation with simulated NMR constraints

“…Computer programs employing a variety of algorithms have been developed to utilize this information for structure determination. These include distance space methods such as metric-matrix distance geometry (DG) (Have1 & Wiithrich, 1984, 1985Hare & Reid, 1986;Lautz et al, 1989) and real space methods such as variable target function algorithms in dihedral angle space (Braun & Go, 1985), restrained molecular dynamics (MD) (Kaptein et al, 1985;Briinger et al, 1986), dynamic simulated annealing (SA) (Nilges et al, 1988), and Monte-Carlo (MC) calculations (Bassolino, 1989;Levy et al, 1989;Ulyanov et al, 1993). The DG methods are purely mathematical procedures, whereas the real space methods 593 include the minimization of a target function that includes both NMR-derived constraints and some form of potential energy function.…”