Employment of MD simulations to study the relation between 3D genome organisation and disease predisposition and treatment

支配基因表达的机制非常复杂，而且受到高度调控。这些机制能够基于许多不同的因素来增加或降低表达水平，这些因素可以是细胞特定的、时间特定的或基于各种外部刺激。此外，长期以来，核内染色质的三维排列一直被证明与基因表达密切相关，对细胞的正确功能至关重要。为了更好地理解驱动DNA折叠的机制，已经采取的一种方法是建立染色质组织的空间模型。这些模型通常利用分子动力学技术，它能够通过积分牛顿运动方程来研究系统的时间动力学。具体地说，可以通过使用聚合物建模模拟来预测染色质结构并生成基因组位置的3D模型，从而使研究染色质纤维的性质与单体结构和化学性质的细节无关。这种方法有很多应用。例如，它可以用来更好地理解表观遗传和3D结构变异在精密医学领域中的作用；事实上，这些因素如何影响疾病的治疗和预防仍未完全揭开面纱。事实上，可以利用生物数据，例如组蛋白修饰中的富集物、染色质可及性信息和芯片序列轨迹，以告知染色质结构的计算机模拟，这可以应用聚合物物理知识来实现。这可能导致识别和描述基因组中显示三维染色质组织变异的区域，目的是获得关于疾病易感性和治疗的新信息。

The mechanisms that govern gene expression are very complex and highly regulated. These mechanisms are capable of increasing or decreasing expression levels based on many diverse factors that can be cell specific, time specific, or based on various external stimuli. Moreover, the three-dimensional arrangement of chromatin within the nucleus has been long shown to be deeply linked to gene expression and crucial for the correct functioning of the cell. In order to reach a better comprehension of the mechanisms that drive the folding of DNA, an approach that has been taken is to develop spatial models of chromatin organisation. These models often make use of Molecular Dynamics techniques, which have the capability of studying the temporal dynamics of a system by integrating Newton's equations of motion. Specifically, it is possible to predict chromatin structure and to generate 3D models of genomic loci through the use of polymer modelling simulations which therefore enables the study chromatin fiber properties irrespectively of the minute details of the monomeric structure and chemical nature. This approach has many applications. For instance, it could be used to gain better understanding of the role of epigenetic and 3D structural variability in the field of Precision Medicine; indeed, how these factors can impact on disease treatment and prevention is still not completely unveiled. It is in fact possible to make use of biological data such as enrichment in histone modifications, chromatin accessibility information and ChIP-seq tracks in order to inform computer simulations of chromatin structure, that can be implemented applying polymer physics knowledge. This could lead to discern and characterise regions within the genome that display variations in three-dimensional chromatin organisation with the purpose of gaining novel information regarding disease predisposition and treatment.