Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
J Am Chem Soc. 2016 Aug 10;138(31):9951-8. doi: 10.1021/jacs.6b05136. Epub 2016 Aug 1.
DNA bending is critical for DNA packaging, recognition, and repair, and occurs toward either the major or the minor groove. The anisotropy of B-DNA groove bending was quantified for eight DNA sequences by free energy simulations employing a novel reaction coordinate. The simulations show that bending toward the major groove is preferred for non-A-tracts while the A-tract has a high tendency of bending toward the minor groove. Persistence lengths were generally larger for bending toward the minor groove, which is thought to originate from differences in groove hydration. While this difference in stiffness is one of the factors determining the overall preference of bending direction, the dominant contribution is shown to be a free energy offset between major and minor groove bending. The data suggests that, for the A-tract, this offset is largely determined by inherent structural properties, while differences in groove hydration play a large role for non-A-tracts. By quantifying the energetics of DNA groove bending and rationalizing the origins of the anisotropy, the calculations provide important new insights into a key biological process.
DNA 弯曲对于 DNA 的包装、识别和修复至关重要，并且发生在大沟或小沟方向。通过使用新的反应坐标进行自由能模拟，对 8 个 DNA 序列的 B-DNA 沟道弯曲各向异性进行了量化。模拟表明，非 A 链倾向于向大沟弯曲，而 A 链有向小沟弯曲的强烈趋势。向小沟弯曲的持久长度通常更大，这被认为源于沟道水合作用的差异。虽然这种刚度差异是决定整体弯曲方向偏好的因素之一，但主要贡献是大沟和小沟弯曲之间的自由能偏移。数据表明，对于 A 链，这种偏移主要由固有结构特性决定，而小沟水合作用的差异在非 A 链中起着重要作用。通过量化 DNA 沟道弯曲的能量学并合理化各向异性的起源，计算为这一关键生物过程提供了重要的新见解。
