Modelling the self-assembly of DNA multi-arm motifs

DNA以其双螺旋结构而闻名。沃森和克里克首先发现了DNA碱基之间非常特殊的相互作用，即腺嘌呤(A)与胸腺嘧啶(T)结合，胞嘧啶(C)与鸟嘌呤(G)结合。这两条链被认为是互补的，因为在每个核苷酸上，碱基以沃森-克里克模式配对（A-T和C-G）。然而，碱基配对的特异性允许除了单双螺旋外的其他结构被编程到一组DNA链中。例如，如果你有三种类型的链，比如P， Q和R，其中P的前半部分与Q的一半互补，后半部分与R的一半互补，而Q和R的其余一半是互补的，这个系统将会形成一个结构，其中三个双螺旋部分在一个连接处相遇。这种基本方法可以按比例放大，在纳米尺度上制造出一整套精确有序的结构，这些结构由互补的DNA分子片段配对的愿望驱动而自我组装。这个领域被称为DNA纳米技术，在本提案中，我们希望研究称为DNA多臂基序的纳米结构。这类结构的三臂例子有点类似于上面提到的连接，除了每条臂是由两个平行的双螺旋组成。通过设计这些图案，使得每个臂上都有短的单链悬垂，这些悬垂与其他臂末端的悬垂互补，这些图案可以形成各种各样的大型结构。例如，根据精确的设计和组装条件，3臂图案可以形成四面体、十二面体和巴基球（所有多面体的3条边在一个顶点相遇）。在实验中，研究人员能够看到他们设计的序列是否成功地组装成目标结构，但无法看到他们是如何做到这一点的。这就是计算机建模和本提案的适用之处。我们想用我们最近开发的技术来模拟DNA，以可视化这些非凡的分子能够如此可靠地自我组装的机制。我们希望获得的见解将对实验学家有很大的帮助，因为这将使他们更好地了解为什么他们的一些设计是成功的，而另一些却没有达到预期的效果。这反过来将帮助他们使设计过程更加合理，从而更有可能成功。希望这将使实验学家能够显著增加他们可以生产的结构类型。

DNA is famous for its double helical structure, in which two strands wide around each other held together by the very specific interactions between the DNA bases that was first discovered by Watson and Crick, namely that adenine (A) bonds with thymine (T) and cytosine (C) bonds with guanine (G). The two strands are said to be complementary, because at each nucleotide the bases pair in the Watson-Crick fashion (A-T, and C-G). However, the specificity of the base pairing allows other structures other than one single double helix to be programmed into a set of DNA strands. For example, if you have 3 types of strands, say P, Q and R, where the first half of P is complement to half of Q, and the second half is complementary to half of R, and the remaining halves of Q and R are complementary, the system will want to form a structure with three double helical sections meeting at a junction. This basic approach can be scaled up to make a whole array of precisely-ordered structures on the nanometer length scale that assemble themselves driven by the desire of complementary stretches of DNA molecules to pair up. This field is called DNA nanotechnology, and in this proposal we wish to study nanostructures called DNA multi-arm motifs. The 3-arm example of this class of structures is somewhat similar to the junction mentioned above, except that each arm is made up of two parallel double helices. By designing these motifs so that there are short single-stranded overhangs at the each of arm that are complementary to the overhangs at the ends of other arms, these motifs can be made to form a whole variety of larger structures. For example, the 3-arm motifs can form tetrahedra, dodecahedra and buckyballs (all polyhedra where 3 edges meet at a vertex) depending on the precise design and the conditions under which they assemble, In experiments, the researchers are able to see if their designed sequences successfully assemble into the target structure, but cannot see how they manage to achieve this. This is where computer modelling and this proposal fits in. We want to use techniques that we recently developed to model DNA to visualize the mechanisms by which these remarkable molecules are able to so reliably self-assemble. The insights that we hope to obtain will be of great help to experimentalists, as it will give them a better idea of why some of their designs are successful whereas others fail to do what is expected. This in turn will help them to make the design procedure more rational and hence more likely to succeed. Hopefully, this will enable the experimentalists to significantly increase the types of structures they can produce.