Scholarlink

<p>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 in favorable cases, where IDP ensembles obtained from different MD force fields are in reasonable initial agreement with experimental data, reweighted ensembles obtained with this approach converge to highly similar conformational distributions. The maximum entropy reweighting procedure presented here facilitates the integration of MD simulations with extensive experimental datasets and demonstrates progress towards the calculation of accurate, force-field independent conformational ensembles of IDPs at atomic resolution.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

查看全文
  • Kaushik Borthakur,
  • Thomas R. Sisk,
  • Francesco P. Panei,
  • Massimiliano Bonomi,
  • Paul Robustelli

摘要

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 in favorable cases, where IDP ensembles obtained from different MD force fields are in reasonable initial agreement with experimental data, reweighted ensembles obtained with this approach converge to highly similar conformational distributions. The maximum entropy reweighting procedure presented here facilitates the integration of MD simulations with extensive experimental datasets and demonstrates progress towards the calculation of accurate, force-field independent conformational ensembles of IDPs at atomic resolution.