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Development of charge-augmented three-point water model (CAIPi3P) for accurate simulations of intrinsically disordered proteins

Lookup NU author(s): Joao Victor de De Souza Cunha, Dr Agnieszka Bronowska



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Intrinsically disordered proteins (IDPs) are molecules without a fixed tertiary structure, exerting crucial roles in cellular signalling, growth and molecular recognition events. Due to their high plasticity, IDPs are very challenging in experim ental and computational structural studies. To provide detailed atomic insight in IDPs’ dynamics governing their functional mechanisms, all-atom molecular dynamics (MD) simulations are widely employed. However, the current generalist force fields and solvent models are unable to generate satisfactory ensembles for IDPs when compared to existing experimental data. In this work, we present a new solvation model, denoted as the ChargeAugmented Three-Point Water Model for Intrinsically Disordered Proteins (CAIPi3P). CAIPi3P has been generated by performing a systematic scan of atomic partial charges assigned to the widely popular molecular scaffold of the three-point TIP3P water model. We found that explicit solvent MD simulations employing CAIPi3P solvation considerably improved the small-angle X-ray scattering (SAXS) scattering profiles for three different IDPs. Not surprisingly, this improvement was further enhanced by using CAIPi3P water in combination with the protein force field parametrized for IDPs. We also demonstrated the applicability of CAIPi3P to molecular systems containing structured as well as intrinsically disordered regions/domains. Our results highlight the crucial importance of solvent effects for generating molecular ensembles of IDPs which reproduce the experimental data available. Hence, we conclude that our newly developed CAIPi3P solvation model is a valuable tool for molecular simulations of intrinsically disordered proteins and assessing their molecular dynamics.

Publication metadata

Author(s): de Souza JV, Zariquiey FS, Bronowska AK

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2020

Volume: 21

Issue: 17

Online publication date: 26/08/2020

Acceptance date: 21/08/2020

Date deposited: 19/11/2020

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI AG


DOI: 10.3390/ijms21176166

PubMed id: 32859072


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