AIChE Annual Meeting
Monday, November 14, 2022 - 3:33pm to 3:54pm
Recent advances in residue-level coarse-grained (CG) computational models for proteins have enabled molecular-level insights into the properties of protein condensates. However, most of the existing CG nucleic acid models include anisotropic potentials between bases that are computationally demanding and are not fully compatible with the existing CG protein models. Here, we present a new CG DNA model that utilizes isotropic potentials between bases and can be used for investigating protein-DNA complexes and nucleosome arrays, thereby enabling a mechanistic understanding of how molecular information is propagated up at the genome level in a computationally tractable manner. To demonstrate the suitability of our model to facilitate large-scale simulations with molecular resolution, we simulate a mono-nucleosomes to generate extensive residue level equilibrium conformational ensembles and provide molecular insights on the role tails of the histone proteins play in influencing the liquid-liquid phase separation (LLPS) of HP1Î± proteins. We find an extensive network of interactions between HP1Î±, DNA, and flexible histone tails in the condensates formed by these different biomolecules, as histone tails favorably interact with DNA influencing the conformational ensemble of the DNA and antagonizes the contacts between HP1Î± and DNA affecting the ability of DNA to promote LLPS of HP1Î±. The findings of this work illuminate the complex molecular framework that contributes to heterochromatin regulation and function.