Computer simulation of polymers in confined and crowded environments

受限和拥挤环境中聚合物的计算机模拟

• 批准号: RGPIN-2016-04955
• 负责人: Polson, James
• 金额: $ 1.97万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681793
• 关键词: Computer; simulation; polymers; confined; crowded

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.**

聚合物是由称为单体的重复化学单元序列组成的链状分子。DNA是聚合物的一个生物学上重要的例子，其单体单元被称为核苷酸。核苷酸序列构成了生物体的遗传信息。近年来，一直存在致力于开发用于操纵和分析DNA的新技术的密集研究活动。这些技术中的许多涉及DNA通过非常紧凑的空间区域的运输。已知聚合物在这些区域中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采样许多不同的分子形状或构象，并且限制减少了可访问构象的数量。因此，构象“熵”（这种构象的数量的量度）减少。另一个称为“自由能”的量随着熵的减少而增加。自由能和聚合物限制的性质之间的关系的基本理解是必不可少的解释实验结果，涉及受限的DNA，从而为DNA分析技术的发展。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染色体（由DNA组成）的分离。据认为，这一过程可能部分是由构象自由能降低的自然趋势驱动的，这受到细菌内部限制的影响。除了限制之外，由于大蛋白质和其他细胞组分而产生的“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力学。* 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，并测试实验系统的理论描述的有效性。我将使用简单的分子模型（使计算可行）来研究聚合物在各种限制条件下对应于那些在DNA实验中使用。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，以及研究大分子拥挤的影响。模拟将主要用于明确计算构象自由能使用各种有效的方法。这些计算结果将有助于（1）为受限聚合物开发更好的理论，（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）更好地理解涉及生物聚合物（如DNA）的细胞过程。