Related Experiment Video
Updated: May 5, 2026
07:33
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
15.8K
Computing the relative stabilities and the per-residue components in protein conformational changes.
Arijit Roy1, Alberto Perez1, Ken A Dill2
1Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA.
Structure (London, England : 1993)
|December 10, 2013
Summary
A new method called confine-convert-release (CCR) calculates protein conformational changes and their driving forces. CCR accurately predicts protein states and identifies key amino acids responsible for transformations.
Area of Science:
- Biophysics
- Computational Biology
- Protein Science
Background:
- Protein molecules exhibit dynamic conformational changes essential for their function.
- Understanding the forces governing these large-scale transformations is crucial for molecular simulations and protein design.
- Existing methods face challenges in accurately predicting stable states for proteins with significant conformational flexibility, such as chameleon sequences.
Purpose of the Study:
- To introduce and validate the "confine-convert-release" (CCR) method for calculating per-residue contributions to conversion free energy.
- To assess the CCR method's ability to predict stable protein states and its performance in protein structure prediction benchmarks.
- To enable the analysis of amino acid contributions to protein conformational changes for improved protein design and mechanism interpretation.
Main Methods:
- Development of the "confine-convert-release" (CCR) computational method.
- Application of CCR to analyze large conformational changes in protein molecules.
- Evaluation of CCR's predictive accuracy using known chameleon sequences and Critical Assessment of Protein Structure Prediction (CASP) data.
Main Results:
- The CCR method successfully predicts stable states for challenging chameleon sequences.
- CCR demonstrates improved discrimination capabilities compared to existing methods in protein structure prediction.
- The method allows for parsing total conversion free energies into per-residue components, identifying key amino acids in transformations.
Conclusions:
- The CCR method provides valuable insights into the forces driving protein conformational changes at the amino acid level.
- CCR facilitates the "reverse-engineering" of design principles for proteins like chameleon sequences.
- This approach holds promise for enhancing protein structure prediction scoring functions, designing novel protein conformational switches, and interpreting protein mechanisms.
Related Concept Videos
01:25Protein Folding
8.8K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.8K
01:22Protein Folding
112.3K
Overview
112.3K
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
992
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...
992
01:24Protein Organization
7.2K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
7.2K
01:49Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K