Bosch David, Campillo Mercedes, Pardo Leonardo
Laboratori de Medicina Computacional, Unitat de Bioestadistica, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
J Comput Chem. 2003 Apr 30;24(6):682-91. doi: 10.1002/jcc.10200.
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 chi 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.
通过分子动力学/平均力势模拟，已计算出PurR、LacI、LEF-1、IHF、Sac7d和Sso7d的蛋白质侧链通过小沟插入使碱基对步弯曲的结构和能量决定因素。弯曲结构的结构决定因素为：两个相邻的呋喃糖环在C3'内（A-DNA）和C2'内（B-DNA）区域呈现不同构象；无论糖的褶皱情况如何，χ扭转角总是取B-DNA的C2'内构象的特征值；蛋白质侧链插入会增加滑动（从负值变为正值）、上升和滚动，并减小扭转。DNA弯曲的能量决定因素为：糖-磷酸主链的构象转变在能量上要求不高；自由能惩罚中碱基间参数的相对重要性依次为滑动、扭转和上升，最后是移动和滚动；侧链插入时滚动的特征性增加和扭转的减少倾向于稳定DNA弯曲过程。
