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

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.