Related Experiment Video
Updated: May 16, 2026
10:50
Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
The dominant folding route minimizes backbone distortion in SH3
Heiko Lammert1, Jeffrey K Noel, José N Onuchic
1Center for Theoretical Biological Physics and Department of Physics, Rice University, Houston, TX, USA.
Plos Computational Biology
|November 21, 2012
Summary
Protein folding mechanisms are shaped by geometry, not chain entropy. Cooperative energetic effects, not chain entropy, drive the preferred folding route in SH3, with off-pathway structures penalized by distortions.
Area of Science:
- Biophysics
- Computational Biology
- Protein Dynamics
Background:
- Protein folding is crucial for cellular function and is influenced by energetic and geometric factors.
- Evolution minimizes energetic frustration, leading to smooth energy landscapes and robust native structures.
- Chain connectivity is recognized as a key element in accurate protein folding models.
Purpose of the Study:
- To investigate the interplay between energetic and geometric influences on protein folding.
- To quantitatively analyze the balance of these factors in the SH3 protein folding mechanism.
- To elucidate the contributions of energy and entropy to the folding pathway.
Main Methods:
- Utilized a structure-based model for protein folding studies.
- Employed minimal energetic frustration to focus on geometric and energetic contributions.
- Decomposed the free energy landscape into energy and entropy components.
Main Results:
- Chain entropy does not dictate the protein folding mechanism.
- A cooperative energetic effect governs the preferred folding route through the transition state.
- Off-pathway structures incur an energy penalty due to backbone and contact pair distortions.
Conclusions:
- The folding mechanism of SH3 is primarily driven by energetic cooperation, not chain entropy.
- Geometric constraints and energetic costs associated with distortions play a critical role in selecting folding pathways.
- This energy cost is a significant factor in the complex balance of interactions governing protein folding routes.
Related Concept Videos
01:25Protein Folding
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...
01:22Protein Folding
Overview
01:22Protein Folding
Overview
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
01:29Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...