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 experimental and computational structural studies. To provide detailed atomic insight in IDPs dynamics governing its functional mechanisms, all-atom molecular dynamics (MD) simulations are widely employed. Although, the current generalist force fields and solvent models are unable to generate satisfactory ensembles for IDPs when compared to existing experimental data. This incapacity of attaining reasonable configurations comes from the biased parameters to proteins with a well-defined tertiary structure. With the development of new and more accurate experimental data for IDPs, improvements of the MD parameters represent a crucial area of research.<br/>Recent developments for parameters have been published, ranging from new force fields and water models, showing significant improvement for unstructured simulations. Here, we present a novel addition to the library of water models to be used for IDPs: The Charge-Augmented 3 Point Water model for Intrinsically-disordered Proteins (CAIPi3P).<br/>CAIPi3P water model was generated through systematic scanning of the dipole moment values calculated upon the TIP3P water model. By increasing the dipole magnitude, the similarity between experimental and calculated SAXS curves are greatly improved.<br/>Using a series of different water model/force field combinations, was seen that more modern combinations improve significantly the similarity between calculated and experimental distributions. The CAIPi3P water model, along with an IDP tailored force field (e.g. AMBER03ws) can calculate a SAXS radial curve with a RMSD between experimental and calculated of 0.0064, while using the well-established TIP3P with AMBER99SB-ILDN attains a value of 0.018.

Development of a novel water model for molecular dynamics for IDPs: Presenting the CAIPi3P model

2019 Fall National Meeting

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