Abstract
Determining accurate atomic resolution conformational ensembles of intrinsically disordered proteins (IDPs) is extremely challenging. Molecular dynamics (MD) simulations provide atomistic conformational ensembles of IDPs, but their accuracy is highly dependent on the quality of physical models, or force fields, used. Here, we demonstrate how to determine accurate atomic resolution conformational ensembles of IDPs by integrating all-atom MD simulations with experimental data from nuclear magnetic resonance (NMR) spectroscopy and small-angle x-ray scattering (SAXS) with a simple, robust and fully automated maximum entropy reweighting procedure. We demonstrate that when this approach is applied with sufficient experimental data, IDP ensembles derived from different MD force fields converge to highly similar conformational distributions. The maximum entropy reweighting procedure presented here facilitates the integration of MD simulations with extensive experimental datasets and enables the calculation of accurate, force-field independent atomic resolution conformational ensembles of IDPs.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The manuscript has been updated to contain an increased emphasis on the properties of the accurate structural ensembles of intrinsically disordered proteins calculated with the new method we propose and to clarify several technical points. Supplemental files were updated. Substantial methodological detail has been moved to the supporting information, and several figures have been swapped from the main text to the SI.
https://github.com/paulrobustelli/Borthakur_MaxEnt_IDPs_2024/