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Related Concept Videos

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR01:15

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.

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Related Experiment Video

Updated: Jun 24, 2026

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion
09:17

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular

Barry J Grant1, Alemayehu A Gorfe, J Andrew McCammon

  • 1Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America. bgrant@mccammon.ucsd.edu

Plos Computational Biology
|March 21, 2009
PubMed
Summary

Ras protein signaling relies on conformational changes between active and inactive states. Accelerated molecular dynamics simulations revealed novel intermediate structures and correlated motions, advancing our understanding of Ras function and its link to cell signaling.

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Computational Biology

Background:

  • Ras proteins are key regulators of cellular signaling pathways.
  • Ras proteins cycle between active (GTP-bound) and inactive (GDP-bound) states.
  • Understanding the dynamics of these conformational changes is crucial for deciphering Ras signaling.

Purpose of the Study:

  • To characterize the nucleotide-dependent conformational transition of Ras.
  • To identify intermediate structures and correlated motions during this transition.
  • To elucidate the complete reaction path of Ras conformational change.

Main Methods:

  • Utilized multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations.
  • Performed classical molecular dynamics (cMD) simulations for comparison.
  • Employed normal mode analysis to study collective motions.

Main Results:

  • Identified highly populated intermediate Ras structures with unique switch and loop conformations.
  • Revealed novel nucleotide-dependent correlated motions between different protein regions.
  • Observed low-frequency collective motion intrinsic to Ras structure during conformational exchange.

Conclusions:

  • The study provides unprecedented insights into the complete reaction path of Ras conformational transitions.
  • Newly identified Ras conformations and correlated motions advance mechanistic understanding of Ras function.
  • Findings highlight a dynamic linkage between the nucleotide-binding site and the C-terminus, critical for Ras signaling.