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

控制基因表达的机制是非常复杂和高度调节的。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异性的、时间特异性的或基于各种外部刺激。此外，核内染色质的三维排列长期以来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，已经采取的方法是开发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，其具有通过整合牛顿运动方程来研究系统的时间动力学的能力。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点的3D模型，从而能够研究染色质纤维性质，而不管单体结构和化学性质的微小细节。这种方法有许多应用。例如，它可以用来更好地了解表观遗传和3D结构变异在精准医学领域的作用;事实上，这些因素如何影响疾病的治疗和预防仍然没有完全揭示。事实上，可以利用生物学数据，如组蛋白修饰的富集，染色质可及性信息和ChIP-seq轨道，以便为染色质结构的计算机模拟提供信息，这可以应用聚合物物理学知识来实现。这可能导致识别和识别基因组内显示三维染色质组织变化的区域，目的是获得有关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.