Related Experiment Video

Updated: Feb 10, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

10.4K

Revealing conformational changes of GTP-bound NRAS mutants probed by GaMD and Markov state models

Lu Zhao1, Jian Wang1, Haipeng Ping2

  • 1School of Science, Shandong Jiaotong University, Jinan, 250357, China. zhaolusdu@163.com.

Physical Chemistry Chemical Physics : PCCP
|February 9, 2026
PubMed

Insights

Oncogenic NRAS mutations alter protein dynamics and internal communication networks. These findings offer insights into aberrant signaling and guide the development of new anti-cancer drugs targeting NRAS (Neuroblastoma RAS).

Area of Science:

  • Molecular biology
  • Biophysics
  • Computational biology

Background:

  • RAS family proteins, including NRAS, are crucial regulators of intracellular signaling pathways.
  • Oncogenic mutations in NRAS can disrupt normal cellular processes like proliferation and survival, contributing to cancer development.

Purpose of the Study:

  • To investigate the conformational dynamics and internal communication networks of wild-type NRAS and its oncogenic mutants (G12D, Q61R, C118S).
  • To understand how specific NRAS mutations impact protein structure and function at a molecular level.

Main Methods:

  • Gaussian accelerated molecular dynamics (GaMD) simulations.
  • Markov state models (MSMs) for analyzing conformational landscapes.
  • Principal component analysis (PCA) and correlation network analysis.

Main Results:

  • NRAS mutations significantly alter the structural dynamics of the switch I and switch II domains.
  • The Q61R mutation was observed to stabilize the overall NRAS conformation.
  • Mutations induce specific changes in the protein's internal communication pathways.

Conclusions:

  • The study provides a detailed mechanistic understanding of how oncogenic NRAS mutations affect protein dynamics.
  • These insights can inform the rational design of targeted anti-cancer therapeutics aimed at aberrant NRAS signaling.

More Related Videos

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

17.3K
Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin10:19

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin

Published on: January 24, 2025

1.1K

Related Concept Videos

Conformity01:20

Conformity

Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
48.2K
Conformations of Butane02:20

Conformations of Butane

Unlike ethane and propane that have only two major conformations, butane has more than two conformers. The staggered form of butane in which the bulky methyl groups on the two carbons are placed on opposite sides, that is, at a dihedral angle of 180°, is the lowest energy, most stable form — called the anti conformer. This conformation is stabilized due to the absence of steric repulsion between the largely spaced out methyl groups. The other two staggered conformations are...
18.2K
Conformations of Cycloalkanes02:29

Conformations of Cycloalkanes

Adolf von Baeyer attempted to explain the instabilities of small and large cycloalkane rings using the concept of angle strain — the strain caused by the deviation of bond angles from the ideal 109.5° tetrahedral value for sp3  hybridized carbons. However, while cyclopropane and cyclobutane are strained, as expected from their highly compressed bond angles, cyclopentane is more strained than predicted, and cyclohexane is virtually strain-free. Hence, Baeyer’s theory that...
14.6K
Conformations of Cyclohexane02:11

Conformations of Cyclohexane

Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
15.8K
Conformations of Ethane and Propane02:18

Conformations of Ethane and Propane

In an organic molecule, free rotation about the carbon-carbon single bond results in energetically different conformers of the molecule. Due to this rotation, called the internal rotation, ethane has two major conformations — staggered and eclipsed.
Staggered conformation is a low energy and more stable conformation with the C-H bonds on the front carbon placed at 60°dihedral angles relative to the C-H bonds on the back carbon, leading to a reduced torsional strain. In staggered...
17.3K
Chair Conformation of Cyclohexane02:02

Chair Conformation of Cyclohexane

The chair conformation is the most stable form of cyclohexane due to the absence of angle and torsional strain. The absence of angle strain is a result of cyclohexane’s bond angle being very close to the ideal tetrahedral bond angle of 109.5° in its chair conformer. Similarly, the torsional strain is also absent owing to the perfectly staggered arrangement of bonds.
The hydrogen atoms linked to carbons are arranged in two different axial and equatorial orientations to achieve this...
18.8K