Assessment of Force Field Accuracy Using Cryogenic Electron Microscopy Data of Hyper-thermostable Glutamate Dehydrogenase

Tomotaka Oroguchi, Mao Oide, Taiki Wakabayashi, Masayoshi Nakasako

研究成果: Article査読

抄録

Molecular dynamics (MD) simulations in biophysically relevant time scales of microseconds is a powerful tool for studying biomolecular processes, but results often display force field dependency. Therefore, assessment of force field accuracy using experimental data of biomolecules in solution is essential for simulation studies. Here, we propose the use of structural models obtained via cryo-electron microscopy (cryoEM), which provides biomolecular structures in vitreous ice mimicking the environment in solution. The accuracy of the AMBER (ff99SB-ILDN-NMR, ff14SB, ff15ipq, and ff15FB) and CHARMM (CHARMM22 and CHARMM36m) force fields was assessed by comparing their MD trajectories with the cryoEM data of thermostable hexameric glutamate dehydrogenase (GDH), which included a cryoEM map at a resolution of approximately 3 Å and structure models of subunits reflecting metastable conformations in domain motion occurring in GDH. In the assessment, we validated the force fields with respect to the reproducibility and stability of secondary structures and intersubunit interactions in the cryoEM data. Furthermore, we evaluated the force fields regarding the reproducibility of the energy landscape in the domain motion expected from the cryoEM data. As a result, among the six force fields, ff15FB and ff99SB-ILDN-NMR displayed good agreement with the experiment. The present study demonstrated the advantages of the high-resolution cryoEM map and suggested the optimal force field to reproduce experimentally observed protein structures.

本文言語English
ページ(範囲)8479-8494
ページ数16
ジャーナルJournal of Physical Chemistry B
124
39
DOI
出版ステータスPublished - 2020 10 1

ASJC Scopus subject areas

  • 物理化学および理論化学
  • 表面、皮膜および薄膜
  • 材料化学

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