Simulating Dynamic Chromosome Compaction: Methods for Bridging In Silico to In Vivo.

ABSTRACT

The application of polymer models to chromosome structure and dynamics is a powerful approach for dissecting functional properties of the chromosome. The models are based on well-established bead-spring models of polymers and are distinct from molecular dynamics studies used in structural biology. In this work, we outline a polymer dynamics model that simulates budding yeast chromatin fibers in a viscous environment inside the nucleus using DataTank as a user interface for the C++ simulation. We highlight features for creating the nucleolus, a dynamic region of chromatin with protein-mediated, transient chromosomal cross-links, providing a predictive, stochastic polymer-physics model for versatile analyses of chromosome spatiotemporal organization. DataTank provides real-time visualization and data analytics methods during simulation. The simulation pipeline provides insights into the entangled chromosome milieu in the nucleus and creates simulated chromosome data, both structural and dynamic, that can be directly compared to experimental observations of live cells in interphase and mitosis.