Using transition density models to interpret experimental optical spectra of exciton-coupled cyanine (iCy3)2 dimer probes of local DNA conformations at or near functional protein binding sites
Using transition density models to interpret experimental optical spectra of exciton-coupled cyanine (iCy3)2 dimer probes of local DNA conformations at or near functional protein binding sites
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DOI：
10.1093/nar/gkad1163
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发表时间：
2023-12-05
影响因子：
14.9
通讯作者：
Marcus，Andrew H.
中科院分区：
文献类型：
--
作者：
Heussman，Dylan;Enkhbaatar，Lulu;Marcus，Andrew H.
激子耦合发色团二聚体是一类新兴的用于研究位点特异性生物分子相互作用的光学探针。应用精确的理论模型描述分子二聚体探针的静电耦合是模拟其光学性质和分析光谱数据的关键步骤。在这项工作中，我们比较实验吸光度和圆二色性（CD）光谱的“内部标记”（iCy3）2二聚体探针插入位点特异性DNA叉结构的理论计算这些激子耦合二聚体的结构和几何形状。我们比较了不同近似水平的跃迁密度模型，以确定（iCy3）2二聚体标记的DNA叉结构的构象参数。通过应用原子上详细的过渡电荷（TQ）模型，我们可以区分二聚体构象，其中平面iCy3单体之间的堆叠和倾斜角是不同的。这种方法的一个主要优点是，我们确定的（iCy3）2二聚体探针的局部构象可以用来推断结构的DNA框架的信息，直接围绕在构建体内的不同位置的探针，无论是在双链体DNA序列的深处，还是在蛋白质复合物结合以释放其生物学功能的DNA叉路口或附近的位点。
Exciton-coupled chromophore dimers are an emerging class of optical probes for studies of site-specific biomolecular interactions. Applying accurate theoretical models for the electrostatic coupling of a molecular dimer probe is a key step for simulating its optical properties and analyzing spectroscopic data. In this work, we compare experimental absorbance and circular dichroism (CD) spectra of ‘internally-labeled’ (iCy3)2dimer probes inserted site-specifically into DNA fork constructs to theoretical calculations of the structure and geometry of these exciton-coupled dimers. We compare transition density models of varying levels of approximation to determine conformational parameters of the (iCy3)2dimer-labeled DNA fork constructs. By applying an atomistically detailed transition charge (TQ) model, we can distinguish between dimer conformations in which the stacking and tilt angles between planar iCy3 monomers are varied. A major strength of this approach is that the local conformations of the (iCy3)2dimer probes that we determined can be used to infer information about the structures of the DNA framework immediately surrounding the probes at various positions within the constructs, both deep in the duplex DNA sequences and at sites at or near the DNA fork junctions where protein complexes bind to discharge their biological functions.