TY - JOUR
T1 - A-Tract bending
T2 - Insights into experimental structures by computational models
AU - Strahs, Daniel
AU - Schlick, Tamar
N1 - Funding Information:
We thank Professor Zippi Shakked for her many invaluable insights. We are indebted to Dr Steve Burley for stimulating the TATA-box variant study (to be detailed elsewhere) and Xiaoliang Qian for performing a large part of the TATA-box simulation work. We are also grateful to Professor Martin Karplus for use of the CHARMM program, Dr Thomas E. Cheatham III for the converted AMBER force field suitable for CHARMM, Professor Richard Lavery for use of the Curves program as well as helpful communications, and Professor Thomas Tullius for providing hydroxyl radical cleavage data and valuable information. Helpful discussions with Drs Wilma Olson, David Beveridge, Matthew Young, and Chris Wiggins are also acknowledged. The work was supported by NIH grant GM55164 and NSF grants BIR-94-23827EQ and ASC-9704681 to T.S. T. Schlick is an investigator of the Howard Hughes Medical Institute.
PY - 2000/8/18
Y1 - 2000/8/18
N2 - While solution structures of adenine tract (A-tract) oligomers have indicated a unique bend direction equivalent to negative global roll (commonly termed 'minor-groove bending'), crystallographic data have not unambiguously characterized the bend direction; nevertheless, many features are shared by all A-tract crystal and solution structures (e.g. propeller twisting, narrow minor grooves, and localized water spines). To examine the origin of bending and to relate findings to the crystallographic and solution data, we analyze molecular dynamics trajectories of two solvated A-tract dodecamers: 1D89, d(CGCGA6CG), and 1D98, d(CGCA6GCG), using a new general global bending framework for analyzing bent DNA and DNA/protein complexes. It is significant that the crystallographically-based initial structures are converted from dissimilar to similar bend directions equivalent to negative global roll, with the average helical-axis bend ranging from 10.5°to 14.1°. The largest bend occurs as positive roll of 12°on the 5' side of the A-tracts (supporting a junction model) and is reinforced by gradual curvature at each A-tract base-pair (bp) step (supporting a wedge model). The precise magnitude of the bend is subtly sequence dependent (consistent with a curved general sequence model). The conversion to negative global· roll only requires small local changes at each bp, accumulated over flexible moieties both outside and inside the A-tract. In contrast, the control sequence 1BNA, d(CGCGA2TTCGCG), bends marginally (only 6.9°) with no preferred direction. The molecular features that stabilize the bend direction in the A-tract dodecamers include propeller twisting of AT base-pairs, puckering differences between A and T deoxyriboses, a narrow minor groove, and a stable water spine (that extends slightly beyond the A-tract, with lifetimes approaching 0.2 ns). The sugar conformations, in particular, are proposed as important factors that support bent DNA. It is significant that all these curvature-stabilizing features are also observed in the crystallographic structures, but yield overall different bending paths, largely due to the effects of sequences outside the A-tract. These results merge structural details reported for A-tract structures by experiment and theory and lead to structural and dynamic insights into sequence-dependent DNA flexibility, as highlighted by the effect of an A-tract variant of a TATA-box element on bending and flexibility required for TBP binding. (C) 2000 Academic Press.
AB - While solution structures of adenine tract (A-tract) oligomers have indicated a unique bend direction equivalent to negative global roll (commonly termed 'minor-groove bending'), crystallographic data have not unambiguously characterized the bend direction; nevertheless, many features are shared by all A-tract crystal and solution structures (e.g. propeller twisting, narrow minor grooves, and localized water spines). To examine the origin of bending and to relate findings to the crystallographic and solution data, we analyze molecular dynamics trajectories of two solvated A-tract dodecamers: 1D89, d(CGCGA6CG), and 1D98, d(CGCA6GCG), using a new general global bending framework for analyzing bent DNA and DNA/protein complexes. It is significant that the crystallographically-based initial structures are converted from dissimilar to similar bend directions equivalent to negative global roll, with the average helical-axis bend ranging from 10.5°to 14.1°. The largest bend occurs as positive roll of 12°on the 5' side of the A-tracts (supporting a junction model) and is reinforced by gradual curvature at each A-tract base-pair (bp) step (supporting a wedge model). The precise magnitude of the bend is subtly sequence dependent (consistent with a curved general sequence model). The conversion to negative global· roll only requires small local changes at each bp, accumulated over flexible moieties both outside and inside the A-tract. In contrast, the control sequence 1BNA, d(CGCGA2TTCGCG), bends marginally (only 6.9°) with no preferred direction. The molecular features that stabilize the bend direction in the A-tract dodecamers include propeller twisting of AT base-pairs, puckering differences between A and T deoxyriboses, a narrow minor groove, and a stable water spine (that extends slightly beyond the A-tract, with lifetimes approaching 0.2 ns). The sugar conformations, in particular, are proposed as important factors that support bent DNA. It is significant that all these curvature-stabilizing features are also observed in the crystallographic structures, but yield overall different bending paths, largely due to the effects of sequences outside the A-tract. These results merge structural details reported for A-tract structures by experiment and theory and lead to structural and dynamic insights into sequence-dependent DNA flexibility, as highlighted by the effect of an A-tract variant of a TATA-box element on bending and flexibility required for TBP binding. (C) 2000 Academic Press.
KW - A-tracts
KW - Molecular dynamics
KW - Narrow minor groove
KW - Sequence-dependent bending
KW - Stable water spine
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U2 - 10.1006/jmbi.2000.3863
DO - 10.1006/jmbi.2000.3863
M3 - Article
C2 - 10966775
AN - SCOPUS:0034682870
SN - 0022-2836
VL - 301
SP - 643
EP - 663
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 3
ER -