Spring Model - Chromatin Modeling Tool Based on OpenMM

Abstract

Chromatin structure modeling is a rapidly developing field. Parallel to the enormous growth of available experimental data, there is a growing need of building and visualizing 3D structures of nuclei, chromosomes, chromatin domains, and single loops associated with particular gene loci. Here, we present a tool for chromatin domain modeling; it is available as a webservice and standalone python script. Our tool is based on molecular mechanics and utilizes the OpenMM engine for model generation. In this method the user provides contacts between chromatin regions and obtains a 3D structure that satisfies them. Additional parameters allow for the control of fibre stiffness, initial structure adjustments and simulation resolution, there are also options for structure refinement and modeling in a spherical container. The user may provide contacts in the form of bead indices, or insert interactions in genome coordinates sourced from BEDPE files. After the simulation is complete, the user is able to download the structure in the Protein Data Bank (PDB) format for further analysis. We dedicate this tool to all who are interested in chromatin structures. It is suitable for quick visualization of datasets, studying the impact of structural variants (SVs), inspecting the effects of adding and removing particular contacts, and measuring features such as maximum distances between sites (e.g.promoter-enhancer), or local chromatin density.

Keywords: 3C; 3D nucleus structure; Biophysical modeling; ChIA-PET; Chromatin 3D modeling; Chromatin higher order structure; Hi-C; Structural variants.