Computer simulation of polymers in confined and crowded environments

聚合物是由一系列重复的化学单元组成的链状分子，称为单体。DNA是一种具有生物学意义的聚合物，其单体单元被称为核苷酸。它是组成生物体遗传信息的核苷酸序列。近年来，致力于开发操纵和分析DNA的新技术的研究活动非常激烈。其中许多技术涉及DNA在空间非常紧凑的区域内的运输。众所周知，聚合物在这些区域的限制会影响它们的物理性质。例如，聚合物的灵活性意味着它们将对许多不同的分子形状或构象进行采样，而限制减少了可接近的构象的数量。因此，构象“熵”(衡量这种构象的数量)减少。另一个被称为“自由能”的量往往会随着熵的减小而增加。基本了解自由能与聚合物限制性质之间的关系，对于解释涉及受限DNA的实验结果，从而开发DNA分析技术是至关重要的。此外，这些信息对于理解自然过程也很有用。一个例子是细菌中复制的染色体(由DNA组成)的分离。有人认为，这一过程可能部分是由构象自由能下降的自然趋势驱动的，而这是受细菌内部限制的影响。除了限制外，大蛋白质和其他细胞成分造成的“拥挤”效应也会影响涉及DNA和其他生物聚合物的其他过程的动态。 我将使用计算机模拟方法来研究限制和拥挤对聚合物自由能的影响。仿真是在计算机上对模型系统进行的虚拟实验。仿真可以用来解释实验结果，并检验实验系统理论描述的有效性。我将使用简单的分子模型(使计算可行)来研究与DNA实验中使用的条件相对应的各种限制条件下的聚合物。我还将研究在类似于细菌内部的限制条件下的聚合物分离，以及调查大分子拥挤的影响。这些模拟将主要用于使用各种有效的方法显式计算构象自由能。这些计算结果将有助于(1)发展更好的受限聚合物理论，(2)理解受限DNA实验中的观察结果，(3)指导DNA分析方法的发展，以及(4)更好地理解涉及DNA等生物聚合物的细胞过程。

Polymers are chain-like molecules composed of a sequence of repeating chemical units called monomers. DNA is a biologically significant example of a polymer, one whose monomeric units are called nucleotides. It is the sequence of the nucleotides that comprises the genetic information of an organism. In recent years, there has been intense research activity devoted to the development of novel technologies for manipulating and analyzing DNA. Many of these technologies involve the transport of DNA through very compact regions of of space. The confinement of polymers in such regions is known to affect their physical properties. For example, the flexibility of polymers means that they will sample many different molecular shapes, or conformations, and confinement reduces the number of accessible conformations. Thus, the conformational "entropy" (a measure of the number of such conformations) decreases. Another quantity called "free energy" tends to increase as the entropy decreases. A basic understanding of the relationship between the free energy and the nature of the confinement of polymers is essential for interpreting the results of experiments involving confined DNA and thus for developing techniques for DNA analysis. In addition, this information is useful for understanding natural processes. One example is the segregation of replicated chromosomes (which are comprised of DNA) in bacteria. It is thought that the process may be driven in part by the natural tendency for the conformational free energy to decrease, and this is affected by the confinement inside the bacterium. In addition to confinement, the effects of "crowding" due to large proteins and other cellular components can also influence the dynamics of other processes involving DNA and other biopolymers. I will use computer simulation methods to study the effects of confinement and crowding on the free energy of polymers. A simulation is a virtual experiment on a model system carried out on a computer. Simulations can be used to interpret the results of experiments and test the validity of theoretical descriptions of experimental systems. I will use simple molecular models (to make the calculations feasible) to study polymers in a variety of confinement conditions corresponding to those used in DNA experiments. I will also study polymer separation under confinement conditions similar to those inside bacteria, as well as investigate the effects of macromolecular crowding. The simulations will be used mainly to explicitly calculate the conformational free energy using a variety efficient methods. These results of the calculations will be useful for (1) developing better theories for confined polymers, (2) understanding observations in confined-DNA experiments, (3) guiding the development of DNA analysis methods, and (4) better understanding cellular processes involving biopolymers such as DNA.