Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

¹H NMR: Interpreting Distorted and Overlapping Signals01:02

¹H NMR: Interpreting Distorted and Overlapping Signals

Spin systems where the difference in chemical shifts of the coupled nuclei is greater than ten times J are called first-order spin systems. These nuclei are weakly coupled, and their chemical shifts and coupling constant can generally be estimated from the well-separated signals in the spectrum.
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are slanted or...
¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)01:20

¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)

When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
2D NMR: Homonuclear Correlation Spectroscopy (COSY)01:06

2D NMR: Homonuclear Correlation Spectroscopy (COSY)

Homonuclear correlation spectroscopy, or COSY, is a 2-dimensional NMR technique that provides information about coupled protons. Typically, the geminal and vicinal coupling are observed. For example, consider the COSY spectrum of ethyl acetate, where its 1D proton NMR spectrum is plotted along the vertical and horizontal axes with their corresponding chemical shift scale. Three spots on the diagonal corresponding to the three peaks in the 1D proton spectrum are called diagonal peaks. The COSY...
¹³C NMR: ¹H–¹³C Decoupling01:04

¹³C NMR: ¹H–¹³C Decoupling

The probability of having two carbon-13 atoms next to each other is negligible because of the low natural abundance of carbon-13. Consequently, peak splitting due to carbon-carbon spin-spin coupling is not observed in spectra. However, protons up to three sigma bonds away split the carbon signal according to the n+1 rule, resulting in complicated spectra.
A broadband decoupling technique is used to simplify these complex, sometimes overlapping, signals. Broadband decoupling relies on a...
Nuclear Overhauser Enhancement (NOE)01:06

Nuclear Overhauser Enhancement (NOE)

Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically bonded or involved in J-coupling. This phenomenon, called the nuclear Overhauser enhancement (NOE), results from through-space interactions between the nuclear spins. The NOE effect decreases with increasing internuclear distance and is generally not observed beyond 4 angstroms. In NOE, dipole-dipole interactions between neighboring spin-active...
Double Resonance Techniques: Overview01:12

Double Resonance Techniques: Overview

Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or radiofrequency pulses to manipulate and observe two distinct nuclear spins. One important application of double resonance is spin decoupling, which selectively suppresses coupling with one type of nucleus while observing the NMR signal from another nucleus, simplifying the spectrum and enhancing resolution.
Spin decoupling is usually achieved by...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Publisher's Note: "Reducing weighted ensemble variance with optimal trajectory management" [J. Chem. Phys. 164, 094110 (2026)].

The Journal of chemical physics·2026
Same author

Reducing weighted ensemble variance with optimal trajectory management.

The Journal of chemical physics·2026
Same author

Microstructural Manipulation for Enhanced Average Thermoelectric Performance: A Case Study of Tin Telluride.

ACS applied materials & interfaces·2025
Same author

Lessons Learned from a Ligand-Unbinding Stress Test for Weighted Ensemble Simulations.

ACS omega·2025
Same author

We are not doing enough: Truth-telling and Aboriginal and Torres Strait Islander history in Australian Public Health.

PLOS global public health·2025
Same author

Helical dislocation-driven plasticity and flexible high-performance thermoelectric generator in α-Mg<sub>3</sub>Bi<sub>2</sub> single crystals.

Nature communications·2025

Related Experiment Video

Updated: May 7, 2026

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
11:11

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing

Published on: August 24, 2017

16.7K

Exploration of Cryptic Pockets Using Enhanced Sampling Along Normal Modes: A Case Study of KRAS G12D.

Neha Vithani1, She Zhang1, Jeffrey P Thompson1

  • 1OpenEye, Cadence Molecular Sciences, Santa Fe, New Mexico 87508, United States.

Journal of Chemical Information and Modeling
|October 17, 2024
PubMed
Summary

This study introduces a new method using molecular dynamics simulations to find hidden cryptic pockets in proteins like KRAS. This approach helps discover new drug targets, especially for challenging mutations in cancer therapy.

More Related Videos

Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions
08:23

Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions

Published on: September 25, 2018

13.1K
Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

5.6K

Related Experiment Videos

Last Updated: May 7, 2026

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
11:11

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing

Published on: August 24, 2017

16.7K
Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions
08:23

Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions

Published on: September 25, 2018

13.1K
Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein
07:08

Fully Processed Recombinant KRAS4b: Isolating and Characterizing the Farnesylated and Methylated Protein

Published on: January 16, 2020

5.6K

Area of Science:

  • Computational chemistry
  • Structural biology
  • Drug discovery

Background:

  • Cryptic pockets are hidden ligand-binding sites in proteins, offering new therapeutic targets.
  • KRAS was considered undruggable due to conserved binding sites, but cryptic pockets present opportunities.
  • The discovery of the Switch-II cryptic pocket in KRASG12C led to approved cancer drugs.

Purpose of the Study:

  • To develop and validate a novel computational approach for identifying cryptic pockets.
  • To explore cryptic pockets in wild type KRAS and the KRASG12D mutant.
  • To investigate the binding mechanisms of inhibitors to cryptic pockets.

Main Methods:

  • Weighted ensemble molecular dynamics simulations with inherent normal modes.
  • Extensive all-atomic simulations (>400 μs) with and without cosolvents (xenon, ethanol, benzene).
  • Analysis of simulation trajectories using three distinct pocket-finding methods.

Main Results:

  • The new approach successfully predicted known cryptic binding sites in KRAS.
  • Simulations provided insights into the nature of cryptic pockets in KRASG12D.
  • Ligand-binding simulations elucidated the role of conformational selection versus induced fit.

Conclusions:

  • The developed method is effective for exploring cryptic pockets in proteins.
  • This approach can aid in discovering novel allosteric binding sites for drug development.
  • Understanding cryptic pocket dynamics is crucial for designing targeted therapies for oncogenic mutations.