Investigation of the Proton-Assisted Pathway to Formation of the Catalytically Active, Ferryl Species of P450s by Molecular Dynamics Studies of P450eryF

1996 ◽  
Vol 118 (27) ◽  
pp. 6377-6387 ◽  
Author(s):  
Danni L. Harris ◽  
Gilda H. Loew
Keyword(s):  
Molecular Dynamics ◽  
Catalytically Active ◽  
Ferryl Species

scholarly journals Molecular Dynamics to Predict Cryo-EM: Capturing Transitions and Short-Lived Conformational States of Biomolecules

2021 ◽  
Vol 8 ◽  
Author(s):  
Łukasz Nierzwicki ◽  
Giulia Palermo
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Atomic Level ◽  
Conformational States ◽  
Variable Regions ◽  
Biologically Relevant ◽  
Active Structure ◽  
Conformational Variability ◽  
Challenges And Opportunities ◽  
Catalytically Active

Single-particle cryogenic electron microscopy (cryo-EM) has revolutionized the field of the structural biology, providing an access to the atomic resolution structures of large biomolecular complexes in their near-native environment. Today’s cryo-EM maps can frequently reach the atomic-level resolution, while often containing a range of resolutions, with conformationally variable regions obtained at 6 Å or worse. Low resolution density maps obtained for protein flexible domains, as well as the ensemble of coexisting conformational states arising from cryo-EM, poses new challenges and opportunities for Molecular Dynamics (MD) simulations. With the ability to describe the biomolecular dynamics at the atomic level, MD can extend the capabilities of cryo-EM, capturing the conformational variability and predicting biologically relevant short-lived conformational states. Here, we report about the state-of-the-art MD procedures that are currently used to refine, reconstruct and interpret cryo-EM maps. We show the capability of MD to predict short-lived conformational states, finding remarkable confirmation by cryo-EM structures subsequently solved. This has been the case of the CRISPR-Cas9 genome editing machinery, whose catalytically active structure has been predicted through both long-time scale MD and enhanced sampling techniques 2 years earlier than cryo-EM. In summary, this contribution remarks the ability of MD to complement cryo-EM, describing conformational landscapes and relating structural transitions to function, ultimately discerning relevant short-lived conformational states and providing mechanistic knowledge of biological function.

Investigating coordination flexibility of glycerophosphodiesterase (GpdQ) through interactions with mono-, di-, and triphosphoester (NPP, BNPP, GPE, and paraoxon) substrates

2019 ◽  
Vol 21 (10) ◽  
pp. 5499-5509 ◽  
Author(s):  
Gaurav Sharma ◽  
Qiaoyu Hu ◽  
Vindi M. Jayasinghe-Arachchige ◽  
Thomas J. Paul ◽  
Gerhard Schenk ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Catalytically Active

Interactions of the catalytically active binuclear form of glycerophosphodiesterase (GpdQ) with chemically diverse substrates, i.e. phosphomono-, phosphodi-, and phosphotriester have been investigated using molecular dynamics (MD) simulations.

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