Comparison of results from different coarse-grained models of Intrinsically Disordered Proteins

Understanding the intricate behavior of intrinsically disordered proteins (IDPs) is essential to make therapeutic interventions for various neurodegenerative diseases. IDPs have been studied with several coarse-grained (CG) models with different levels of granularity, which are expected to reveal information at different length scales. We present simulation results from three different CG models^1,2,3,4 (HPS1, HPS2, and SOP-IDP). The first two are slight variants of the models studied earlier by Dignon et al. [2] and Tesei et al. [3] studied by us [1] which use different hydropathy scales. The SOP-IDP model, on the contrary, is slightly different from HPS1 and HPS2 in that it is based on a three-parameter model with the inclusion of a sidechain for 18 amino acids. We compare results from different models with the experimental gyration radii [5] to understand the relative merits of these models.

¹Swarnadeep Seth, Brandon Stine, and Aniket Bhattacharya, “Fine structures of Intrinsically Disordered Proteins”. (2023), ArXiv: https://doi.org/10.48550/arXiv.2307.16383

²Gregory L. Dignon, Wenwei Zheng, Young C. Kim, Robert B. Best, and Jeetain Mittal, “Sequence determinants of protein phase behavior from a coarse-grained model”. PLOS Computational Biology 14, e1005941 (2018).

³Giulio Tesei, Thea K Schulze, Ramon Crehuet, and Kresten Lindorff-Larsen, “Accurate model of liquid-liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties”. Proceedings of the National Academy of Sciences 118, (2021).

⁴Upayan Baul, Debayan Chakraborty, Mauro L Mugnai, John E Straub, and D Thirumalai, “Sequence Effects on Size, Shape, and Structural Heterogeneity in Intrinsically Disordered Proteins”. The Journal of Physical Chemistry B 123, 3462-3474 (2019).

⁵Thomas Dannenhoffer-Lafage and Robert B. Best, “A Data-Driven Hydrophobicity Scale for Predicting Liquid-Liquid Phase Separation of Proteins”. J. Phys. Chem. B 125, 4046-4056 (2021).