Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism

Ngo, Van A.

doi:10.13139/OLCF/2396898

Title: Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism

Dataset
Other Related Research

Abstract

This study presents the first large-scale simulation using an initial structure predicted by AI/ML algorithms for the 648-amino-acid CRaf kinase, which plays a key role in cellular signaling. Simulation results show the evolution of the predicted structure into much more compact structures with inter-domain interactions that shed insights into auto-inhibition mechanism, paradoxical effect, activation, and recruitment pathways in the CRaf kinase. Newly identified epitopes in the CRaf may suggest additional drug targets. The results were published in Biophysical Journal, DOI:10.1016/j.bpj.2024.06.028.

Authors:

Ngo, Van A.

ORNL-OLCF

Publication Date:: Fri Jul 26 04:00:00 UTC 2024

Research Org.:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Org.:: Office of Science (SC); Office of Science (SC), Advanced Scientific Computing Research (ASCR) (SC-21)

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Biophysics, Cellular Signaling, Molecular Dynamics Simulations, Signalosome

OSTI Identifier:: 2396898

DOI:: https://doi.org/10.13139/OLCF/2396898

Citation Formats


                    Ngo, Van A. Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism.  United States: N. p., 2024. 
        Web.  doi:10.13139/OLCF/2396898.

Copy to clipboard


                    Ngo, Van A. Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism.  United States.  doi:https://doi.org/10.13139/OLCF/2396898

Copy to clipboard


                    Ngo, Van A. 2024.  
"Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism".  United States.  doi:https://doi.org/10.13139/OLCF/2396898.  https://www.osti.gov/servlets/purl/2396898. Pub date:Fri Jul 26 04:00:00 UTC 2024

Copy to clipboard


                    
@article{osti_2396898,

  title        = {Insight into Molecular Basis and Dynamics of Full-length CRaf Kinase in Cellular Signaling Mechanism},

  author       = {Ngo, Van A.},

  abstractNote = {This study presents the first large-scale simulation using an initial structure predicted by AI/ML algorithms for the 648-amino-acid CRaf kinase, which plays a key role in cellular signaling. Simulation results show the evolution of the predicted structure into much more compact structures with inter-domain interactions that shed insights into auto-inhibition mechanism, paradoxical effect, activation, and recruitment pathways in the CRaf kinase. Newly identified epitopes in the CRaf may suggest additional drug targets. The results were published in Biophysical Journal, DOI:10.1016/j.bpj.2024.06.028.},

  doi          = {10.13139/OLCF/2396898},

  journal      = {},

  number       = ,

  volume       = ,

  place        = {United States},

  year         = {Fri Jul 26 04:00:00 UTC 2024},

  month        = {Fri Jul 26 04:00:00 UTC 2024}

}

Copy to clipboard

Dataset:

View Dataset

DOI: https://doi.org/10.13139/OLCF/2396898

Save / Share:

Export Metadata

Save to My Library

Similar records in DOE Data Explorer and OSTI.GOV collections:

Insight into molecular basis and dynamics of full-length CRaf kinase in cellular signaling mechanisms

Journal Article Ngo, Van A. - Biophysical Journal

Raf kinases play key roles in signal transduction in cells for regulating proliferation, differentiation, and survival. Despite decades of research into functions and dynamics of Raf kinases with respect to other cytosolic proteins, understanding Raf kinases is limited by the lack of their full-length structures at the atomic resolution. Here, we present the first model of the full-length CRaf kinase obtained from artificial intelligence/machine learning algorithms with a converging ensemble of structures simulated by large-scale temperature replica exchange simulations. Our model is validated by comparing simulated structures with the latest cryo-EM structure detailing close contacts among three key domains andmore »« less
Data and Code for Atomic Scale Etching of Diamond: Insights from Molecular Dynamics Simulations

Dataset Draney, Jack S. ; Vella, Joseph R. ; Panagiotopoulos, Athanassios Z. ; ...

This work investigates the effects of argon ions, hydrogen atoms, and hydrogen ions on the diamond (100) surface using classical molecular dynamics simulations. The purpose of this investigation was to asses plasma processing techniques for applications in quantum device manufacturing. The simulations suggest that combining argon ion smoothing with selective, near threshold energy H removal of amorphous C could be an effective strategy for diamond surface engineering, leading to more reliable and sensitive diamond color center devices. Results were found to differ significantly with interatomic potential, and an analysis of these differences was also carried out. Included in this repositorymore »« less
Full-length transcriptional unit mapping during cellulosic ethanologenesis by bacteria.

Dataset grass, jeff
Structural insights into the mechanism of rhodopsin phosphodiesterase

Dataset Ikuta, Tatsuya

Crystal structures of TMD of Rhodopsin phosphodiesterase (Rh-PDE). 6160 small-wedge (10°/crystal) datasets collected from loop-harvested microcrystals using EIGER X 9M detector at a wavelength of 1 Å on BL32XU, SPring-8. Beam size was around 15×10 µm2 and oscillation step was 0.1°. The crystals belonged to space group P212121 with unit cell parameters a~66, b~74, c~117 Å. 864 datasets were indexed and integrated using XDS with KAMO pipeline. Finally 271 integrated results were merged at 2.6 Å resolution after CC-based clustering and outlier rejection by KAMO in the published result.
Full Rod Length Gamma Spectroscopy Measurements of LWR Used Fuel Rods

Dataset Smith, Susan K

Twenty-five high-burnup pressurized water reactor used fuel rods were scanned in the Irradiated Fuels Examination Laboratory at Oak Ridge National Laboratory with a high-resolution gamma spectrometer. A planar high-purity germanium detector was used across an energy range from 60 keV to 3 MeV. Gamma spectra of individual fuel rods were collected in 4.5 mm steps along the entire length of each rod. Additional spectra were collected on select rods in rotational increments of 30 degrees to provide data on the distribution of fission products along the rod perimeter.

Similar Records